Experimental cell research最新文献

英文中文

Epic, classic, and remarkable: 75 years of Experimental Cell Research

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-21 DOI: 10.1016/j.yexcr.2025.114447

Ji-Long Liu (Editor-in-Chief)

引用次数: 0

Human umbilical cord mesenchymal stem cell-derived exosome ameliorate doxorubicin-induced senescence

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-21 DOI: 10.1016/j.yexcr.2025.114450

Zhen Yang , Feng Yan , Jiangwei Yuan , Manjun Yang , Jinyu Wang , Changqiao You , Kaiqun Ren

Background

Cellular senescence refers to a condition where cells permanently cease division while maintaining metabolic activity. Doxorubicin (Dox) is known as an agent of induction of cellular senescence. This study aimed to explore the potential role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) in mitigating Dox induced senescent.

Method

NIH3T3 cells were treated by various concentrations of Dox with or without hucMSC-Exo, cell morphology, viability, migration, senescence-associated SA-β-Gal staining were monitored. Cellular senescence was induced in C57BL/6J mice via administration of 5 mg/kg Doxorubicin, followed by treatment with hucMSC-Exo or metformin. Assessments included body weight, liver and kidney weight, colon length, SA-β-Gal staining of kidney and skin, molecular biomarkers of aging such as p16^INK4A, p53, and p21^Waf1/Clip1 to evaluate senescence status.

Result

We found that after the treatment of exosomes or metformin improved several aging-related phenotypes in both mouse and cellular models, including increases in body weight, liver and kidney weights, and the reduction of SA-β-Gal positive cells in kidney and skin tissues as well as cell models. At the molecular level, hucMSC-Exo resulted in the downregulation of inflammatory factors and senescence markers in liver and kidney tissues as well as cell models.

Conclusion

Our study demonstrates hucMSC-Exo may ameliorate Dox induced senescence either in NIH3T3 cells or in mice.

背景：细胞衰老是指细胞在保持新陈代谢活动的同时永久停止分裂的一种状态。众所周知，多柔比星（Dox）是诱导细胞衰老的一种药物。本研究旨在探索人脐带间充质干细胞衍生的外泌体（hucMSC-Exo）在缓解Dox诱导的衰老中的潜在作用：方法：用不同浓度的Dox处理NIH3T3细胞，加入或不加入hucMSC-Exo，监测细胞形态、活力、迁移、衰老相关的SA-β-Gal染色。给 C57BL/6J 小鼠注射 5 mg/kg 多柔比星，然后用 hucMSC-Exo 或二甲双胍处理，诱导细胞衰老。评估包括体重、肝脏和肾脏重量、结肠长度、肾脏和皮肤的 SA-β-Gal 染色、衰老的分子生物标志物（如 p16INK4A、p53 和 p21Waf1/Clip1），以评估衰老状态：结果：我们发现，外泌体或二甲双胍处理后，小鼠和细胞模型中与衰老相关的几种表型都得到了改善，包括体重、肝脏和肾脏重量的增加，肾脏、皮肤组织和细胞模型中SA-β-Gal阳性细胞的减少。在分子水平上，hucMSC-Exo导致肝脏和肾脏组织以及细胞模型中的炎症因子和衰老标志物下调：我们的研究表明，hucMSC-Exo 可改善 NIH3T3 细胞或小鼠中由 Dox 引起的衰老。

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引用次数: 0

microRNA-30c attenuates contrast-induced acute kidney injury by reducing renal tubular epithelial cell apoptosis via targeting SOCS1

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-20 DOI: 10.1016/j.yexcr.2025.114456

Long Peng , Yanting Luo , Fang Tan , Qian Chen , Jiafu Wang , Xiaolan Ouyang , Bingyuan Wu , Xixiang Tang , Suhua Li

Contrast-induced acute kidney injury (CIAKI) is a common complication after contrast media administration. Growing evidences implicate microRNA (miR)-30c has a key role in renal diseases. This study aimed to investigate the role and mechanism of miR-30c in CIAKI. CIAKI rat models were established using tail vein injection of omnipaque. MiR-30c was significantly downregulated in CIAKI models both in vivo and in vitro, concomitant with increased cell apoptosis and deteriorated renal injury. Meanwhile, the cell apoptosis, renal dysfunction and renal injury under contrast exposure were alleviated after overexpression of miR-30c. Mechanistically, we demonstrated that miR-30c directly targeted SOCS1, whose downregulation reduced contrast-induced HK-2 cell apoptosis. Furthermore, the upregulation of SOCS1 abolish the protective effect of the overexpression of miR-30c on contrast-induced cell apoptosis. In summary, overexpression of miR-30c inhibited renal tubular epithelial cell apoptosis and mitigated CIAKI via inhibiting the gene of SOCS1.

{"title":"microRNA-30c attenuates contrast-induced acute kidney injury by reducing renal tubular epithelial cell apoptosis via targeting SOCS1","authors":"Long Peng , Yanting Luo , Fang Tan , Qian Chen , Jiafu Wang , Xiaolan Ouyang , Bingyuan Wu , Xixiang Tang , Suhua Li","doi":"10.1016/j.yexcr.2025.114456","DOIUrl":"10.1016/j.yexcr.2025.114456","url":null,"abstract":"<div><div>Contrast-induced acute kidney injury (CIAKI) is a common complication after contrast media administration. Growing evidences implicate microRNA (miR)-30c has a key role in renal diseases. This study aimed to investigate the role and mechanism of miR-30c in CIAKI. CIAKI rat models were established using tail vein injection of omnipaque. MiR-30c was significantly downregulated in CIAKI models both in vivo and in vitro, concomitant with increased cell apoptosis and deteriorated renal injury. Meanwhile, the cell apoptosis, renal dysfunction and renal injury under contrast exposure were alleviated after overexpression of miR-30c. Mechanistically, we demonstrated that miR-30c directly targeted SOCS1, whose downregulation reduced contrast-induced HK-2 cell apoptosis. Furthermore, the upregulation of SOCS1 abolish the protective effect of the overexpression of miR-30c on contrast-induced cell apoptosis. In summary, overexpression of miR-30c inhibited renal tubular epithelial cell apoptosis and mitigated CIAKI via inhibiting the gene of SOCS1.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114456"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476027","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

H50Q mutation in alpha-Synuclein impairs the insulin signaling pathway and induces neuroinflammation in the Drosophila model

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-20 DOI: 10.1016/j.yexcr.2025.114460

Pooja Rai , Rakesh Kumar

H50Q mutations in the SNCA gene, also known as also known as the alpha-Synuclein (α-Syn), have been causally linked to familial Parkinson's disease (PD). PD is primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra region of the brain.α-Syn- plays a pivotal role in the formation of Lewy bodies (LB), a prominent pathological marker in PD. Growing evidence has highlighted the involvement of the insulin signaling pathway dysfunction in various neurodegenerative models. This study aimed to explore how the H50Q mutation in α-Syn influences the insulin signaling pathway and the overall lifespan of fruit flies afflicted with PD. It has been established that a mutation in α-Syn affects mitochondrial function and increases oxidative stress, ultimately contributing to the death of dopaminergic neurons. The impairment of mitochondrial function disrupts metabolism and exerts an adverse effect on the insulin signaling pathway. Furthermore, the unfolded protein response of the endoplasmic reticulum (ER) are investigated and observed a decrease in the expression of PERK (Protein kinase R-like ER kinase) during ER stress. These findings confirm the intricate interplay between the insulin signaling pathway and the activation of the PERK-ER stress pathway. However, the degeneration of neurons triggers a neuroinflammatory response, which are found to be mitigated by the improvement of insulin signaling and the PERK-ER stress-related pathway. The results of this studyshed light on the novel regulatory role of PERK within the insulin signaling pathway and suggest its potential as a therapeutic candidate for modulating neuroinflammation in the context of α-Syn -associated PD pathology.

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引用次数: 0

Perspectives of exosomal ncRNAs in the treatment of bone metabolic diseases: Focusing on osteoporosis, osteoarthritis, and rheumatoid arthritis

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-20 DOI: 10.1016/j.yexcr.2025.114457

Daodi Qiu , Binghan Yan , Haipeng Xue , Zhanwang Xu , Guoqing Tan , Yajuan Liu

Bone metabolic disorders, constituting a group of prevalent and grave conditions, currently have a scarcity of therapeutic alternatives. Over the recent past, exosomes have been at the forefront of research interest, owing to their nanoparticulate nature and potential for therapeutic intervention. ncRNAs are a class of heterogeneous transcripts that they lack protein-encoding capacity, yet they can modulate the expression of other genes through multiple mechanisms. Mounting evidence underscores the intricate role of exosomes as ncRNAs couriers implicated in the pathogenesis of bone metabolic disorders. In this review, we endeavor to elucidate recent insights into the roles of three ncRNAs – miRNAs, lncRNAs, and circRNAs – in bone metabolic ailments such as osteoporosis, osteoarthritis, and rheumatoid arthritis. Additionally, we examine the viability of exosomal ncRNAs as innovative, cell-free modalities in the diagnosis and therapeutic management of bone metabolic disorders. We aim to uncover the critical function of exosomal ncRNAs within the context of bone metabolic diseases.

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引用次数: 0

PD98059 inhibit the proliferation and differentiation of osteoblasts in the formation of tympanosclerosis via ERK1/2-MAPK signaling pathway

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-20 DOI: 10.1016/j.yexcr.2025.114437

Yu Huang, Wenxia Huang, Gengtian Liang, Dou Liu, Chenhui He, Longkai Xiao, Xianting Gao

Tympanosclerosis (TS) has become a common pathological condition of the middle ear, but the underlying mechanism of it is still ambiguous. It was found that osteoprotegerin/receptor activator of nuclear factor kappa B ligand (OPG/RANKL) axis played an important role in the development of TS and was regulated by the extracellular signal regulated kinase 1/2-mitogen activated protein kinase (ERK1/2-MAPK) pathway. However, whether ERK1/2-MAPK pathway mediates the occurrence of TS by regulating OPG/RANKL axis has not been reported. In this study, MAPK and calcium pathway were found significantly activated in TS model. In vivo, the expression of p-ERK1/2 in TS model was significantly increased. In vitro, osteoblasts were isolated from auditory vesicles of neonatal rats for the first time, and then cultured with ERK1/2-MAPK pathway inhibitor PD98059. As results, PD98059 showed inhibitory effects on the phosphorylation of ERK1/2 and proliferation of osteoblasts. Besides, different concentrations of PD98059 showed different inhibitory effects on mRNA expression of osteocalcin (Ocn), bone sialoprotein (Bsp), runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (Bmp2) and OPG. Therefore, it was speculated that the ERK1/2-MAPK pathway may affect the formation of TS by regulating the proliferation and differentiation of osteoblasts, which may be helpful for the study of drug target for tympanosclerosis.

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引用次数: 0

Maternal protein restriction impairs intestinal morphophysiology and antioxidant system in young male offspring rats 母体蛋白质限制会损害幼年雄性后代大鼠的肠道形态生理学和抗氧化系统

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-20 DOI: 10.1016/j.yexcr.2025.114464

Isabela Baptista Leal dos Santos , Matheus Naia Fioretto , Miguel Silingardi Jorge , Luísa Annibal Barata , Isabelle Tenori Ribeiro , André Matheus Leandro Franzolin , Erick Guilherme Stoppa , Renato Mattos , Luiz Marcos Frediane Portela , Maycon Tavares Emílio Silva , Sérgio Alexandre Alcântara dos Santos , José Ricardo de Arruda Miranda , Clélia Akiko Hiruma Lima , Luis Antonio Justulin

The developmental origins of health and disease (DOHaD) concept suggests that adverse conditions during gestation can influence the development and function of multiple organs, including the gastrointestinal tract. Maternal protein restriction (MPR) exposure has been associated with negative effects on reproduction, the endocrine system, and liver metabolic health. However, limited research has explored the impact of MPR on the offspring's intestinal morphophysiology. This study investigated the effects of gestational and lactational MPR on the duodenum and colon of young male offspring rats at postnatal (PND)21. We hypothesize that MPR affects intestinal morphophysiology and development early in life. Our findings revealed tachygastria in offspring exposed to MPR. The ultrastructural analysis uncovered a reduction in goblet cell numbers and changes in collagen deposition in the duodenum and colon. We also identified imbalances in inflammatory markers (IL-6 and TGF-β1) and antioxidant enzymes (CAT and SOD). These results demonstrate that MPR significantly affects gastrointestinal morphophysiology early in life by disrupting gastric motility and altering duodenal and colonic histoarchitecture, antioxidant defense, and inflammatory pathways. Such alterations may predispose the descendants to long-term gastrointestinal disorders, underscoring the importance of further research on the developmental origins of intestinal health and disease.

{"title":"Maternal protein restriction impairs intestinal morphophysiology and antioxidant system in young male offspring rats","authors":"Isabela Baptista Leal dos Santos , Matheus Naia Fioretto , Miguel Silingardi Jorge , Luísa Annibal Barata , Isabelle Tenori Ribeiro , André Matheus Leandro Franzolin , Erick Guilherme Stoppa , Renato Mattos , Luiz Marcos Frediane Portela , Maycon Tavares Emílio Silva , Sérgio Alexandre Alcântara dos Santos , José Ricardo de Arruda Miranda , Clélia Akiko Hiruma Lima , Luis Antonio Justulin","doi":"10.1016/j.yexcr.2025.114464","DOIUrl":"10.1016/j.yexcr.2025.114464","url":null,"abstract":"<div><div>The developmental origins of health and disease (DOHaD) concept suggests that adverse conditions during gestation can influence the development and function of multiple organs, including the gastrointestinal tract. Maternal protein restriction (MPR) exposure has been associated with negative effects on reproduction, the endocrine system, and liver metabolic health. However, limited research has explored the impact of MPR on the offspring's intestinal morphophysiology. This study investigated the effects of gestational and lactational MPR on the duodenum and colon of young male offspring rats at postnatal (PND)21. We hypothesize that MPR affects intestinal morphophysiology and development early in life. Our findings revealed tachygastria in offspring exposed to MPR. The ultrastructural analysis uncovered a reduction in goblet cell numbers and changes in collagen deposition in the duodenum and colon. We also identified imbalances in inflammatory markers (IL-6 and TGF-β1) and antioxidant enzymes (CAT and SOD). These results demonstrate that MPR significantly affects gastrointestinal morphophysiology early in life by disrupting gastric motility and altering duodenal and colonic histoarchitecture, antioxidant defense, and inflammatory pathways. Such alterations may predispose the descendants to long-term gastrointestinal disorders, underscoring the importance of further research on the developmental origins of intestinal health and disease.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114464"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471263","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

HOXD8 drives Glioma progression through epithelial-mesenchymal transition regulation: Implications for prognosis and targeted therapy

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-19 DOI: 10.1016/j.yexcr.2025.114476

Ke Yu , Jiawei Meng , Tiange Chen , Yanshi Wang , Yi Zhao , Tianxiang Huang , Ge Gao

Glioma is one of the most common primary malignant tumors of the central nervous system. Here, we defined Homeobox D8 (HOXD8) as a novel biomarker for glioma utilizing RNA-sequencing and bioinformatics approaches. HOXD8 expression was significantly upregulated in glioma cell lines (U251 and U373) and clinical specimens compared to normal controls. Functional studies demonstrated that HOXD8 knockdown markedly inhibited glioma cell proliferation, migration, and invasion in vitro. Additionally, pan-cancer analysis revealed significant associations between HOXD8 expression and key tumor characteristics, including immune cell infiltratio, tumor mutational burde, and microsatellite instability. Meanwhile, transcriptomic profiling and pathway analysis identified HOXD8's involvement in epithelial-mesenchymal transition (EMT) regulation, with Western blot validation showing significant modulation of EMT markers following HOXD8 knockdown. Collectively, our results suggests that HOXD8 may serve as a satisfactory prognostic biomarker that promotes glioma cell proliferation, migration and invasion, potentially through regulation of EMT processes.

胶质瘤是中枢神经系统最常见的原发性恶性肿瘤之一。在这里，我们利用RNA测序和生物信息学方法将Homeobox D8（HOXD8）定义为胶质瘤的新型生物标志物。与正常对照组相比，HOXD8在胶质瘤细胞系（U251和U373）和临床标本中的表达明显上调。功能研究表明，在体外敲除 HOXD8 能明显抑制胶质瘤细胞的增殖、迁移和侵袭。此外，泛癌分析显示，HOXD8的表达与免疫细胞浸润、肿瘤突变和微卫星不稳定性等关键肿瘤特征之间存在显著关联。同时，转录组分析和通路分析发现，HOXD8参与了上皮-间质转化（EMT）的调控，Western印迹验证显示，敲除HOXD8后，EMT标记物会发生显著变化。总之，我们的研究结果表明，HOXD8可能是一种令人满意的预后生物标志物，它可能通过调控EMT过程促进胶质瘤细胞的增殖、迁移和侵袭。

{"title":"HOXD8 drives Glioma progression through epithelial-mesenchymal transition regulation: Implications for prognosis and targeted therapy","authors":"Ke Yu , Jiawei Meng , Tiange Chen , Yanshi Wang , Yi Zhao , Tianxiang Huang , Ge Gao","doi":"10.1016/j.yexcr.2025.114476","DOIUrl":"10.1016/j.yexcr.2025.114476","url":null,"abstract":"<div><div>Glioma is one of the most common primary malignant tumors of the central nervous system. Here, we defined Homeobox D8 (HOXD8) as a novel biomarker for glioma utilizing RNA-sequencing and bioinformatics approaches. HOXD8 expression was significantly upregulated in glioma cell lines (U251 and U373) and clinical specimens compared to normal controls. Functional studies demonstrated that HOXD8 knockdown markedly inhibited glioma cell proliferation, migration, and invasion <em>in vitro</em>. Additionally, pan-cancer analysis revealed significant associations between HOXD8 expression and key tumor characteristics, including immune cell infiltratio, tumor mutational burde, and microsatellite instability. Meanwhile, transcriptomic profiling and pathway analysis identified HOXD8's involvement in epithelial-mesenchymal transition (EMT) regulation, with Western blot validation showing significant modulation of EMT markers following HOXD8 knockdown. Collectively, our results suggests that HOXD8 may serve as a satisfactory prognostic biomarker that promotes glioma cell proliferation, migration and invasion, potentially through regulation of EMT processes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114476"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467505","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

Targeted inhibition of NPR3/MAPK pathway enhances dental pulp stem cell multipotency: Mechanistic validation based on ligustrazine (TMP)

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-19 DOI: 10.1016/j.yexcr.2025.114479

Hailiang Cui , Yeying Zhang , Huiling Liang , Lizheng Wu

Background

The multipotency of dental pulp stem cells (DPSCs) plays a crucial role in dental tissue regeneration, yet its regulatory mechanisms remain incompletely understood. This study aimed to investigate the role of natriuretic peptide receptor 3 (NPR3) in regulating DPSCs functions and validate the mechanism of its targeted inhibitor ligustrazine (TMP).

Methods

NPR3 expression in DPSCs was examined by Western blot and immunohistochemistry. The effects of NPR3 on DPSCs colony formation, migration, and differentiation were investigated through overexpression and knockdown strategies. The relationship between NPR3 and ERK1/2 pathway was explored using molecular biological approaches. High-throughput drug screening was employed to identify TMP as an NPR3 inhibitor, followed by mechanism validation.

Results

NPR3 was highly expressed in mature odontogenic DPCs, with its expression levels closely correlated with DPSCs functions. Functional assays demonstrated that NPR3 inhibited DPSCs colony formation, migration, and differentiation capabilities, while NPR3 knockdown significantly enhanced these functions. Mechanistic studies revealed that NPR3 influenced DPSCs functions through positive regulation of ERK1/2 phosphorylation. Through high-throughput screening, we identified TMP as a specific NPR3 inhibitor that promoted DPSCs functions. Rescue experiments further confirmed that NPR3 overexpression or ERK1/2 inhibitor SCH772984 attenuated TMP-induced enhancement, validating TMP's action through the NPR3/MAPK pathway.

Conclusion

This study reveals the crucial role of the NPR3/MAPK pathway in regulating DPSCs multipotency and demonstrates that TMP enhances DPSCs functions through targeted inhibition of this pathway, providing new therapeutic strategies and drug targets for dental tissue regeneration.

{"title":"Targeted inhibition of NPR3/MAPK pathway enhances dental pulp stem cell multipotency: Mechanistic validation based on ligustrazine (TMP)","authors":"Hailiang Cui , Yeying Zhang , Huiling Liang , Lizheng Wu","doi":"10.1016/j.yexcr.2025.114479","DOIUrl":"10.1016/j.yexcr.2025.114479","url":null,"abstract":"<div><h3>Background</h3><div>The multipotency of dental pulp stem cells (DPSCs) plays a crucial role in dental tissue regeneration, yet its regulatory mechanisms remain incompletely understood. This study aimed to investigate the role of natriuretic peptide receptor 3 (NPR3) in regulating DPSCs functions and validate the mechanism of its targeted inhibitor ligustrazine (TMP).</div></div><div><h3>Methods</h3><div>NPR3 expression in DPSCs was examined by Western blot and immunohistochemistry. The effects of NPR3 on DPSCs colony formation, migration, and differentiation were investigated through overexpression and knockdown strategies. The relationship between NPR3 and ERK1/2 pathway was explored using molecular biological approaches. High-throughput drug screening was employed to identify TMP as an NPR3 inhibitor, followed by mechanism validation.</div></div><div><h3>Results</h3><div>NPR3 was highly expressed in mature odontogenic DPCs, with its expression levels closely correlated with DPSCs functions. Functional assays demonstrated that NPR3 inhibited DPSCs colony formation, migration, and differentiation capabilities, while NPR3 knockdown significantly enhanced these functions. Mechanistic studies revealed that NPR3 influenced DPSCs functions through positive regulation of ERK1/2 phosphorylation. Through high-throughput screening, we identified TMP as a specific NPR3 inhibitor that promoted DPSCs functions. Rescue experiments further confirmed that NPR3 overexpression or ERK1/2 inhibitor SCH772984 attenuated TMP-induced enhancement, validating TMP's action through the NPR3/MAPK pathway.</div></div><div><h3>Conclusion</h3><div>This study reveals the crucial role of the NPR3/MAPK pathway in regulating DPSCs multipotency and demonstrates that TMP enhances DPSCs functions through targeted inhibition of this pathway, providing new therapeutic strategies and drug targets for dental tissue regeneration.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114479"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464276","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

Development of a biomarker panel for cell characterization intended for cultivated meat

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-18 DOI: 10.1016/j.yexcr.2025.114467

Marc Auguet-Lara, Stig Skrivergaard, Margrethe Therkildsen, Martin Krøyer Rasmussen , Jette Feveile Young

Cultivated meat has in recent years been suggested as a sustainable alternative to produce meat at large-scale. Several aspects of cultivated meat production have demonstrated significant progress. However, there are still many questions regarding the cell culture, media composition, and the production itself to be answered and optimized. Finding good starter cell populations is a challenge to address and requires robust tools to characterize the cell populations. Detailed analysis is required to identify each type of cell within the skeletal muscle niche leads to optimized cultivated meat production at large-scale. In this study, we developed a set of biomarkers, using digital droplet PCR (ddPCR) and Immunofluorescence (IF) staining, to identify specific cell types within a heterogeneous cell population isolated from skeletal muscle tissue. We showed that combining Neural Cell Adhesion Molecule (NCAM), Calponin 1 (CNN1), and Fibronectin (FN), can be a powerful approach to predict the growth of skeletal myotubes, smooth muscle mesenchymal cells (SMMCs), and myofibroblasts, respectively. Moreover, early cell-cell interactions of fibroblastic cells were observed to be triggered through thin actin filaments containing CNN1 protein, to form, subsequently, myofibroblast networks. Besides, Myogenic Differentiation 1 (MyoD) is the key marker to detect skeletal muscle growth, whereas Myogenic Factor 5 (MyF5) can be expressed in myogenic and non-myogenic cells. MyF5 was detected at differentiation stages within the myotube nuclei, suggesting an unknown role during myotube formation.

{"title":"Development of a biomarker panel for cell characterization intended for cultivated meat","authors":"Marc Auguet-Lara, Stig Skrivergaard, Margrethe Therkildsen, Martin Krøyer Rasmussen , Jette Feveile Young","doi":"10.1016/j.yexcr.2025.114467","DOIUrl":"10.1016/j.yexcr.2025.114467","url":null,"abstract":"<div><div>Cultivated meat has in recent years been suggested as a sustainable alternative to produce meat at large-scale. Several aspects of cultivated meat production have demonstrated significant progress. However, there are still many questions regarding the cell culture, media composition, and the production itself to be answered and optimized. Finding good starter cell populations is a challenge to address and requires robust tools to characterize the cell populations. Detailed analysis is required to identify each type of cell within the skeletal muscle niche leads to optimized cultivated meat production at large-scale. In this study, we developed a set of biomarkers, using digital droplet PCR (ddPCR) and Immunofluorescence (IF) staining, to identify specific cell types within a heterogeneous cell population isolated from skeletal muscle tissue. We showed that combining Neural Cell Adhesion Molecule (NCAM), Calponin 1 (CNN1), and Fibronectin (FN), can be a powerful approach to predict the growth of skeletal myotubes, smooth muscle mesenchymal cells (SMMCs), and myofibroblasts, respectively. Moreover, early cell-cell interactions of fibroblastic cells were observed to be triggered through thin actin filaments containing CNN1 protein, to form, subsequently, myofibroblast networks. Besides, Myogenic Differentiation 1 (MyoD) is the key marker to detect skeletal muscle growth, whereas Myogenic Factor 5 (MyF5) can be expressed in myogenic and non-myogenic cells. MyF5 was detected at differentiation stages within the myotube nuclei, suggesting an unknown role during myotube formation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 1","pages":"Article 114467"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445719","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}

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