Experimental cell research最新文献_第6页

A new mechanism in steroid-induced osteonecrosis of the femoral head and the protective role of simvastatin

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114471

Xu-huan Li , Shi-da Qian , Dan Chen , Zhou-zhou Li , Kai-yun Chen , Yong-ping Pan , Xiu-hua Lv , Run-qing Jia , Xue-feng Yu

Objective

Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating bone condition associated with femoral head collapse and hip joint dysfunction. The pathogenesis of SONFH is still not fully elucidated. This study aims to explore the role of mitochondrial cardiolipin metabolism disruption in SONFH and the potential protective effects of simvastatin (SIM).

Methods

Osteoblasts were cultured in vitro under high concentrations of dexamethasone (DEX) to mimic the effects of glucocorticoid exposure seen in SONFH. Mitochondrial structural changes and cardiolipin distribution were examined using transmission electron microscopy and confocal microscopy. Osteoblast proliferation and apoptosis were assessed using CCK-8 assays and flow cytometry. Mitochondrial cardiolipin content was quantified by ELISA, while cytochrome c (Cyt-c) expression was measured through Western blotting. Mitochondrial staining with NAO was analyzed using confocal microscopy and flow cytometry.

Results

DEX exposure led to mitochondrial cardiolipin metabolism disorder and redistribution, resulting in significant mitochondrial structural damage. This disruption was associated with increased release of Cyt-c into the cytoplasm, which correlated with heightened osteoblast apoptosis. SIM treatment mitigated these effects, reducing osteoblast apoptosis by preserving mitochondrial function and modulating cardiolipin content and distribution.

Conclusion

This study demonstrates, for the first time, that glucocorticoid-induced disruptions in mitochondrial cardiolipin metabolism contribute to the pathogenesis of SONFH by inducing Cyt-c release and subsequent osteoblast apoptosis. SIM exerts a protective effect by preserving mitochondrial integrity and function, offering a potential therapeutic avenue for treating hormone-induced osteoblast damage in SONFH.

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引用次数: 0

Exploring mitonuclear interactions in the regulation of cell physiology: Insights from interspecies cybrids

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114466

Kateryna Gaertner , Riikka Tapanainen , Sina Saari , Zsófia Fekete , Steffi Goffart , Jaakko L.O. Pohjoismäki , Eric Dufour

Brown hares (Lepus europaeus) and mountain hares (Lepus timidus) frequently hybridize in regions where their range overlaps, producing fertile offspring and enabling gene flow between the species. Despite this, no hybrid species has emerged, suggesting that hybrid backcrosses may incur fitness costs. One potential mechanism for such costs involves the interactions between mitochondrial and nuclear gene products, where incompatibilities between species-specific alleles may reinforce species barriers and lead to hybrid breakdown. However, direct experimental evidence for this hypothesis remains limited.

In this study, we used fibroblasts derived from skin biopsies of wild-caught hares to generate cytoplasmic hybrid (cybrid) cell lines, wherein mitochondria and mtDNA from one species were transferred to mitochondria-depleted cells of the other species, creating novel mitonuclear gene combinations while preserving the original diploid nuclear background. Employing a range of techniques – including transcriptomics, metabolomics, microscopy, and respirometry – we explored the consequences of mitochondrial transfer between these hare species. Our results reveal that in the studied species mitonuclear incompatibilities exhibit strong effects on cellular fitness but are limited to specific genotypes. We propose mechanisms of cellular-level incompatibility and their potential consequences for interspecific hybrids, offering new insights into the complexity of mitonuclear interactions.

褐兔（Lepus europaeus）和山兔（Lepus timidus）经常在其分布区重叠的地区杂交，产生可育后代，实现物种间的基因流动。尽管如此，仍未出现杂交物种，这表明杂交回交可能会产生适应成本。造成这种代价的一个潜在机制涉及线粒体和核基因产物之间的相互作用，在这种情况下，物种特异性等位基因之间的不相容性可能会加强物种障碍，导致杂交破裂。然而，这一假设的直接实验证据仍然有限。在这项研究中，我们利用从野生野兔皮肤活检中提取的成纤维细胞生成细胞质杂交（细胞杂交）细胞系，将一个物种的线粒体和mtDNA转移到另一个物种的线粒体缺失细胞中，在保留原始二倍体核背景的同时创造出新的有丝分裂核基因组合。我们采用了一系列技术--包括转录组学、代谢组学、显微镜和呼吸测定法--探索了线粒体在这些野兔物种之间转移的后果。我们的研究结果表明，在所研究的物种中，线粒体核不相容对细胞适应性有很大影响，但仅限于特定的基因型。我们提出了细胞水平不相容的机制及其对种间杂交的潜在后果，为有丝分裂核相互作用的复杂性提供了新的见解。

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引用次数: 0

TRIM22 inhibits the metastasis of colorectal cancer through facilitating β-Catenin degradation

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114473

Haiyang Hu, Wensheng Li, Pengfei Ma, Junxin Song, Xiaobo Zhang, Longhui Ruan, Jing Zhang, Youwei Zheng

Tripartite motif-containing 22 (TRIM22), a member of the tripartite motif protein family, has emerged as a putative tumor suppressor in various cancers. Nevertheless, its specific role and clinical significance in colorectal cancer (CRC) remain poorly characterized. Herein, we observed that TRIM22 expression was frequently downregulated in primary CRC tissues and was significantly correlated with better prognosis. Functional assays demonstrated that TRIM22 overexpression substantially attenuated the metastatic potential of CRC cells both in vitro and in vivo. Mechanistically, our results revealed that TRIM22 directly interacts with and ubiquitinates β-Catenin, a crucial transcription factor that drives CRC metastasis by modulating the epithelial-mesenchymal transition (EMT) process. Additionally, our data indicated that the anti-metastatic effect of TRIM22 relies on the degradation of β-catenin. In summary, this study is the first to deliberate the vital anti-tumor role of TRIM22 in CRC metastasis. We also provide new evidence suggesting that TRIM22 could be a prognostic marker and therapeutic target for inhibiting CRC progression.

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引用次数: 0

A genome-wide CRISPR-Cas9 knockout screen using dynamin knockout cells identifies Nf2 and Traf3 as genes involved in dynamin-independent endocytosis

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114470

Sho Takahashi, Mizuho Maehara, Chihiro Nishihara, Hiroyuki Iwata, Shusaku Shibutani

Endocytosis is a fundamental process by which cells take up extracellular materials, including nutrients, growth factors, and pathogens. Although several endocytic pathways, such as clathrin-mediated and caveolin-mediated endocytosis, are well-characterized, other endocytic pathways remain poorly understood. Therefore, in this study, we performed a genome-wide CRISPR-Cas9 screen to elucidate new endocytic pathways using dynamin conditional knockout cells. We identified genes that significantly reduced the cell numbers when knocked out simultaneously with dynamin. Among these, neurofibromin 2 (Nf2) and tumor necrosis factor receptor-associated factor 3 (Traf3), whose relationship with endocytosis was not well understood, were investigated for their roles in endocytosis activity. Nf2 and Traf3 knockout cells exhibited reduced non-specific fluid endocytosis in a dynamin-independent manner. However, Nf2 or Traf3 knockout did not affect the transferrin receptor-mediated endocytosis that depends on clathrin and dynamin. Moreover, Nf2 knockout cells showed reduced cholera toxin uptake in a dynamin-independent manner. Overall, this study highlights the roles of Nf2 and Traf3 in endocytosis.

内吞是细胞吸收细胞外物质（包括营养物质、生长因子和病原体）的基本过程。虽然一些内吞途径，如凝胶蛋白介导的内吞和洞穴素介导的内吞，已经得到了很好的表征，但对其他内吞途径仍然知之甚少。因此，在本研究中，我们进行了一次全基因组的 CRISPR-Cas9 筛选，利用 dynamin 条件性基因敲除细胞来阐明新的内吞途径。我们发现了与达因明同时敲除时细胞数量明显减少的基因。其中，神经纤维瘤蛋白 2（Nf2）和肿瘤坏死因子受体相关因子 3（Traf3）与内吞活动的关系尚不十分清楚，我们研究了它们在内吞活中的作用。敲除 Nf2 和 Traf3 的细胞表现出非特异性液体内吞减少，其方式与动态蛋白无关。然而，Nf2或Traf3基因敲除并不影响转铁蛋白受体介导的、依赖于凝集素和达因明的内吞作用。此外，Nf2基因敲除细胞显示出霍乱毒素摄取的减少，而这种摄取是不依赖于动态蛋白的。总之，这项研究强调了Nf2和Traf3在内吞中的作用。

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引用次数: 0

Allograft inflammatory Factor-1 induces the dedifferentiation of Vascular Smooth Muscle cells into a macrophage-like phenotype both in vivo and in vitro

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114475

Ruoyu Dong , Jikuan Li , Guangwei Jiang , Yunjie Tian , Wei Bi

Atherosclerosis, a chronic lipid-driven vascular inflammatory disease involving multiple cell types, is the primary cause of cardiovascular disease-related morbidity and mortality. Allograft inflammatory factor 1 (AIF-1) contributes to atherosclerosis development by affecting vascular smooth muscle cells (VSMCs). Increasing research indicates that VSMCs are pivotal in atherosclerosis progression, particularly in macrophage-like phenotypic switching, though the mechanism of AIF-1 VSMCs phenotypic switching is not well understood. This study aims to correlate AIF-1 expression with atherosclerosis development and VSMCs phenotypic switching. AIF-1 was expressed in the atherosclerotic plaques of patients with carotid artery narrowing and atherosclerosis mice. AIF-1 was expressed in ox-LDL treated VSMCs and promoted the apoptosis of VSMCs. AIF-1 significantly influenced macrophage-like VSMC numbers through the AIF-1/NF-κB pathway, enhancing lipid uptake and TNF-α and IL-6 secretion. This study showed increased AIF-1 expression in atherosclerotic plaques in both patients with carotid stenosis and an atherosclerosis animal model. AIF-1 facilitated VSMC dedifferentiation into macrophage-like cells, enhancing lipid uptake and inflammatory factor release through the AIF-1/NF-κB pathway.

{"title":"Allograft inflammatory Factor-1 induces the dedifferentiation of Vascular Smooth Muscle cells into a macrophage-like phenotype both in vivo and in vitro","authors":"Ruoyu Dong , Jikuan Li , Guangwei Jiang , Yunjie Tian , Wei Bi","doi":"10.1016/j.yexcr.2025.114475","DOIUrl":"10.1016/j.yexcr.2025.114475","url":null,"abstract":"<div><div>Atherosclerosis, a chronic lipid-driven vascular inflammatory disease involving multiple cell types, is the primary cause of cardiovascular disease-related morbidity and mortality. Allograft inflammatory factor 1 (AIF-1) contributes to atherosclerosis development by affecting vascular smooth muscle cells (VSMCs). Increasing research indicates that VSMCs are pivotal in atherosclerosis progression, particularly in macrophage-like phenotypic switching, though the mechanism of AIF-1 VSMCs phenotypic switching is not well understood. This study aims to correlate AIF-1 expression with atherosclerosis development and VSMCs phenotypic switching. AIF-1 was expressed in the atherosclerotic plaques of patients with carotid artery narrowing and atherosclerosis mice. AIF-1 was expressed in ox-LDL treated VSMCs and promoted the apoptosis of VSMCs. AIF-1 significantly influenced macrophage-like VSMC numbers through the AIF-1/NF-κB pathway, enhancing lipid uptake and TNF-α and IL-6 secretion. This study showed increased AIF-1 expression in atherosclerotic plaques in both patients with carotid stenosis and an atherosclerosis animal model. AIF-1 facilitated VSMC dedifferentiation into macrophage-like cells, enhancing lipid uptake and inflammatory factor release through the AIF-1/NF-κB pathway.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114475"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering significances of autophagy in the development and metabolism of adipose tissue

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114478

Zitao Liu , Haoyuan Peng , Pengfei Liu , Feiyi Duan , Yutian Yang , Pengkun Li , Zhihao Li , Jiaoyan Wu , Jiayi Chang , Dandan Shang , Qiwen Tian , Jiawei Zhang , Yucheng Xie , Zhenzhen Liu , Yang An

The mechanisms of adipose tissue activation and inactivation have been a hot topic of research in the last decade, from which countermeasures have been attempted to be found against obesity as well as other lipid metabolism-related diseases, such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. Autophagy has been shown to be closely related to the regulation of adipocyte activity, which is involved in the whole process including white adipocyte differentiation/maturation and brown or beige adipocyte generation/activation. Dysregulation of autophagy in adipose tissue has been demonstrated to be associated with obesity. On this basis, we summarize the pathways and mechanisms of autophagy involved in the regulation of lipid metabolism and present a review of its pathophysiological roles in lipid metabolism-related diseases, in the hope of providing ideas for the treatment of these diseases.

{"title":"Deciphering significances of autophagy in the development and metabolism of adipose tissue","authors":"Zitao Liu , Haoyuan Peng , Pengfei Liu , Feiyi Duan , Yutian Yang , Pengkun Li , Zhihao Li , Jiaoyan Wu , Jiayi Chang , Dandan Shang , Qiwen Tian , Jiawei Zhang , Yucheng Xie , Zhenzhen Liu , Yang An","doi":"10.1016/j.yexcr.2025.114478","DOIUrl":"10.1016/j.yexcr.2025.114478","url":null,"abstract":"<div><div>The mechanisms of adipose tissue activation and inactivation have been a hot topic of research in the last decade, from which countermeasures have been attempted to be found against obesity as well as other lipid metabolism-related diseases, such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. Autophagy has been shown to be closely related to the regulation of adipocyte activity, which is involved in the whole process including white adipocyte differentiation/maturation and brown or beige adipocyte generation/activation. Dysregulation of autophagy in adipose tissue has been demonstrated to be associated with obesity. On this basis, we summarize the pathways and mechanisms of autophagy involved in the regulation of lipid metabolism and present a review of its pathophysiological roles in lipid metabolism-related diseases, in the hope of providing ideas for the treatment of these diseases.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114478"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NRF-1 promotes FUNDC1-mediated mitophagy as a protective mechanism against hypoxia-induced injury in cardiomyocytes

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114472

Junliang Li , Hui Li , Nan Niu , Yazhou Zhu , Siyu Hou , Wei Zhao

Hypoxia-induced apoptosis and mitochondrial dysfunction in cardiomyocytes are involved in the mechanisms of heart failure. Our previous studies have confirmed that NRF-1 alleviates hypoxia-induced injury by promoting mitochondrial function and inhibiting apoptosis in cardiomyocytes. However, the mechanism by which NRF-1 attenuates hypoxia-induced injury in cardiomyocytes is still unclear. Mitophagy, a selective autophagy, has recently shown a remarkable correlation with hypoxia-induced cardiomyocyte injury. In this study, we evaluated whether NRF-1 protects cardiomyocytes from hypoxia-induced injury by regulating mitophagy. The findings indicate that hypoxia prevents H9c2 cells from growing, encourages mitochondrial dysfunction, and triggers mitophagy. In addition, promoting mitophagy by rapamycin reduces hypoxia-induced injury in H9c2 cells. Overexpression of NRF-1 in hypoxia-induced H9c2 cells promotes mitophagy and alleviates cell injury, and this effect can be inhibited by 3-MA. Further study found that NRF-1 promotes the expression of FUNDC1 by binding to its promoter region. Knockdown of FUNDC1 in NRF-1 over-expression H9c2 cells inhibited mitophagy and aggravated hypoxia-induced injury. In conclusion, our study suggests that NRF-1 protects against hypoxia-induced injury by regulating FUNDC1-mediated mitophagy in cardiomyocytes.

{"title":"NRF-1 promotes FUNDC1-mediated mitophagy as a protective mechanism against hypoxia-induced injury in cardiomyocytes","authors":"Junliang Li , Hui Li , Nan Niu , Yazhou Zhu , Siyu Hou , Wei Zhao","doi":"10.1016/j.yexcr.2025.114472","DOIUrl":"10.1016/j.yexcr.2025.114472","url":null,"abstract":"<div><div>Hypoxia-induced apoptosis and mitochondrial dysfunction in cardiomyocytes are involved in the mechanisms of heart failure. Our previous studies have confirmed that NRF-1 alleviates hypoxia-induced injury by promoting mitochondrial function and inhibiting apoptosis in cardiomyocytes. However, the mechanism by which NRF-1 attenuates hypoxia-induced injury in cardiomyocytes is still unclear. Mitophagy, a selective autophagy, has recently shown a remarkable correlation with hypoxia-induced cardiomyocyte injury. In this study, we evaluated whether NRF-1 protects cardiomyocytes from hypoxia-induced injury by regulating mitophagy. The findings indicate that hypoxia prevents H9c2 cells from growing, encourages mitochondrial dysfunction, and triggers mitophagy. In addition, promoting mitophagy by rapamycin reduces hypoxia-induced injury in H9c2 cells. Overexpression of NRF-1 in hypoxia-induced H9c2 cells promotes mitophagy and alleviates cell injury, and this effect can be inhibited by 3-MA. Further study found that NRF-1 promotes the expression of FUNDC1 by binding to its promoter region. Knockdown of FUNDC1 in NRF-1 over-expression H9c2 cells inhibited mitophagy and aggravated hypoxia-induced injury. In conclusion, our study suggests that NRF-1 protects against hypoxia-induced injury by regulating FUNDC1-mediated mitophagy in cardiomyocytes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114472"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EBP50 regulates senescence and focal adhesion in endometrial carcinoma

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-17 DOI: 10.1016/j.yexcr.2025.114465

Ako Yokoi , Ryoya Ogomori , Yasuko Oguri, Miki Hashimura, Makoto Saegusa

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) is a multifunctional scaffold protein that is highly expressed in polarized epithelial cells. Here, we focused on the functional roles of EBP50 in endometrial carcinoma (Em Ca). We analyzed immunohistochemical sections from 121 Em Ca and 30 normal samples. We also characterized EBP50 overexpression or knockout (KO) Em Ca cell lines. High levels of membranous (Me) EBP50 expression were observed in endometrial tissues from normal menstrual cycles, in contrast to the transient upregulation of cytoplasmic (Cyt) EBP50 in tissues in the proliferative phase; this was probably in response to estrogenic effects. There was a significant stepwise reduction of Me-EBP50 expression from grade (G) 1 to G3 Em Cas, which was consistent with the loss of glandular structures. Conversely, Cyt-EBP50 levels increased with in the higher tumor grades. Low Me-EBP50 expression was significantly associated with tumor lymphovascular invasion and short overall survival. Whereas EBP50 KO led to senescence and reduced proliferation and motility, overexpression elicited the opposite phenotypes. Moreover, the number of focal adhesions (FAs), which mediate cell migration, was significantly increased in EBP50 overexpressing cells but decreased in the KO cells. In conclusion, Me- and/or Cyt-EBP50 expression contributes to acceleration of cell motility through enhancement of FA formation, and inhibits senescence to promote cytokinesis. Together, these effects contribute to Em Ca aggressiveness.

{"title":"EBP50 regulates senescence and focal adhesion in endometrial carcinoma","authors":"Ako Yokoi , Ryoya Ogomori , Yasuko Oguri, Miki Hashimura, Makoto Saegusa","doi":"10.1016/j.yexcr.2025.114465","DOIUrl":"10.1016/j.yexcr.2025.114465","url":null,"abstract":"<div><div>Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) is a multifunctional scaffold protein that is highly expressed in polarized epithelial cells. Here, we focused on the functional roles of EBP50 in endometrial carcinoma (Em Ca). We analyzed immunohistochemical sections from 121 Em Ca and 30 normal samples. We also characterized EBP50 overexpression or knockout (KO) Em Ca cell lines. High levels of membranous (Me) EBP50 expression were observed in endometrial tissues from normal menstrual cycles, in contrast to the transient upregulation of cytoplasmic (Cyt) EBP50 in tissues in the proliferative phase; this was probably in response to estrogenic effects. There was a significant stepwise reduction of Me-EBP50 expression from grade (G) 1 to G3 Em Cas, which was consistent with the loss of glandular structures. Conversely, Cyt-EBP50 levels increased with in the higher tumor grades. Low Me-EBP50 expression was significantly associated with tumor lymphovascular invasion and short overall survival. Whereas EBP50 KO led to senescence and reduced proliferation and motility, overexpression elicited the opposite phenotypes. Moreover, the number of focal adhesions (FAs), which mediate cell migration, was significantly increased in EBP50 overexpressing cells but decreased in the KO cells. In conclusion, Me- and/or Cyt-EBP50 expression contributes to acceleration of cell motility through enhancement of FA formation, and inhibits senescence to promote cytokinesis. Together, these effects contribute to Em Ca aggressiveness.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114465"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endoplasmic reticulum stress and unfolded protein response in renal lipid metabolism

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-17 DOI: 10.1016/j.yexcr.2025.114463

Xinyi Zhou , Ziyi Li , Fajian Ren , Hua Deng , Jiayu Wen , Qiwen Xiang , Zhihui Zhou , Xiyun Yang , Chaolong Rao

The endoplasmic reticulum (ER) is a crucial cellular organelle involved in protein synthesis, folding, modification, and transport. Exposure to internal and external stressors can induce endoplasmic reticulum stress (ERS), leading to abnormal protein folding and ER malfunction. This stress can disrupt lipid synthesis, metabolism, and transport processes. Fatty acid oxidation is the primary energy source for the renal system. When energy intake exceeds the storage capacity of adipose tissue, lipids accumulate abnormally in non-adipose tissues, including kidneys, liver, and pancreas. Lipids accumulate in the kidneys of nearly all cell types, including thylakoid membranous, pedunculated, and proximal renal tubular epithelial cells. Intracellular free fatty acids can significantly disrupt renal lipid metabolism, contributing to ischemia-reperfusion acute kidney injury, diabetic nephropathy, renal fibrosis, and lupus nephritis. Consequently, this study delineated the primary signaling pathways and mechanisms of the ERS-induced unfolded protein response, explored the mechanistic link between ERS and lipid metabolism, and elucidated its role in renal lipid metabolism. This study aimed to offer new perspectives on managing and treating renal disorders.

{"title":"Endoplasmic reticulum stress and unfolded protein response in renal lipid metabolism","authors":"Xinyi Zhou , Ziyi Li , Fajian Ren , Hua Deng , Jiayu Wen , Qiwen Xiang , Zhihui Zhou , Xiyun Yang , Chaolong Rao","doi":"10.1016/j.yexcr.2025.114463","DOIUrl":"10.1016/j.yexcr.2025.114463","url":null,"abstract":"<div><div>The endoplasmic reticulum (ER) is a crucial cellular organelle involved in protein synthesis, folding, modification, and transport. Exposure to internal and external stressors can induce endoplasmic reticulum stress (ERS), leading to abnormal protein folding and ER malfunction. This stress can disrupt lipid synthesis, metabolism, and transport processes. Fatty acid oxidation is the primary energy source for the renal system. When energy intake exceeds the storage capacity of adipose tissue, lipids accumulate abnormally in non-adipose tissues, including kidneys, liver, and pancreas. Lipids accumulate in the kidneys of nearly all cell types, including thylakoid membranous, pedunculated, and proximal renal tubular epithelial cells. Intracellular free fatty acids can significantly disrupt renal lipid metabolism, contributing to ischemia-reperfusion acute kidney injury, diabetic nephropathy, renal fibrosis, and lupus nephritis. Consequently, this study delineated the primary signaling pathways and mechanisms of the ERS-induced unfolded protein response, explored the mechanistic link between ERS and lipid metabolism, and elucidated its role in renal lipid metabolism. This study aimed to offer new perspectives on managing and treating renal disorders.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114463"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HSPD1-facilitated formation of CTPS cytoophidia promotes proliferation in C2C12 cells

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-17 DOI: 10.1016/j.yexcr.2025.114462

Lili Liu , Wen Chen , Haijing Luo , Weiwei Zhang , Zhenzhu Zhang , Xin Huang , Xuepeng Fu

CTP synthase (CTPS) is a rate-limiting enzyme that controls CTP synthesis and can polymerize to form a filamentous structure called cytoophidia. The presence of cytoophidia affects the enzymatic activity of CTPS. However, whether CTPS can form cytoophidia in C2C12 cells and whether it affects the proliferation of skeletal muscle satellite cells needs to be further studied. In this study, we found that CTPS could form cytoophidia during C2C12 cell proliferation, and that overexpression of CTPS significantly promoted the formation of CTPS cytoophidia and increased the viability and proliferation rate of C2C12 cells. However, the CTPS H355A mutation hindered the formation of CTPS cytoophidia and inhibited the viability and proliferation of C2C12 cells. In addition, we found that the HSPD1 protein could interact with the CTPS protein and interference with Hspd1 gene expression inhibited the formation of CTPS cytoophidia, even with the overexpression of the CTPS gene. Subsequently, it inhibited C2C12 cells proliferation. Thus, these findings reveal the role of CTPS cytoophidia formation in C2C12 cells proliferation.

{"title":"HSPD1-facilitated formation of CTPS cytoophidia promotes proliferation in C2C12 cells","authors":"Lili Liu , Wen Chen , Haijing Luo , Weiwei Zhang , Zhenzhu Zhang , Xin Huang , Xuepeng Fu","doi":"10.1016/j.yexcr.2025.114462","DOIUrl":"10.1016/j.yexcr.2025.114462","url":null,"abstract":"<div><div>CTP synthase (CTPS) is a rate-limiting enzyme that controls CTP synthesis and can polymerize to form a filamentous structure called cytoophidia. The presence of cytoophidia affects the enzymatic activity of CTPS. However, whether CTPS can form cytoophidia in C2C12 cells and whether it affects the proliferation of skeletal muscle satellite cells needs to be further studied. In this study, we found that CTPS could form cytoophidia during C2C12 cell proliferation, and that overexpression of <em>CTPS</em> significantly promoted the formation of CTPS cytoophidia and increased the viability and proliferation rate of C2C12 cells. However, the CTPS H355A mutation hindered the formation of CTPS cytoophidia and inhibited the viability and proliferation of C2C12 cells. In addition, we found that the HSPD1 protein could interact with the CTPS protein and interference with <em>Hspd1</em> gene expression inhibited the formation of CTPS cytoophidia, even with the overexpression of the <em>CTPS</em> gene. Subsequently, it inhibited C2C12 cells proliferation. Thus, these findings reveal the role of CTPS cytoophidia formation in C2C12 cells proliferation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114462"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0