Cellular signalling最新文献_第4页

The roles of IDH2 and glutathione metabolism in cetuximab resistance in head and neck squamous cell carcinoma investigated by metabolomics and transcriptomics

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-20 DOI: 10.1016/j.cellsig.2025.111620

Shousen Hu , Zian Wang , Xu Ding , Daoke Yao , Yue Du , Xiangzhen Kong

Cetuximab resistance is a significant challenge in the treatment of head and neck squamous cell carcinoma (HNSCC). In this study, cetuximab-resistant HNSCC cell lines were established, and untargeted metabolomics was used to detect differences in metabolite profiles between sensitive and resistant cell lines. It was found that glutathione metabolism significantly differed between the sensitive and resistant lines. Combining these findings with transcriptome data, correlation analysis of metabolites revealed that IDH2 regulated glutathione metabolism and contributed to cetuximab resistance in FaDu cells. In vitro experiments showed that IDH2 was highly expressed in FaDu-CR cells, and IDH2 knockdown significantly enhanced the sensitivity of FaDu and FaDu-CR cells to cetuximab. IDH2 knockdown reduced GSH levels and GPX4 expression in FaDu and FaDu-CR cells under cetuximab treatment, while increasing lipid ROS levels. In vivo experiments demonstrated that IDH2 knockdown decreased the tumorigenic ability of FaDu-CR cells in nude mice treated with cetuximab, as well as reduced GPX4 and Ki67 levels in tumor tissues. In conclusion, IDH2 regulated glutathione metabolism and contributed to cetuximab resistance in HNSCC. This study explores strategies to ameliorate cetuximab resistance in HNSCC preclinical models, providing new insights for reversing cetuximab resistance in HNSCC.

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引用次数: 0

METTL14-mediated m6A modification of TRPA1 promotes acute visceral pain induced by uterine cervical dilation by promoting NR2B phosphorylation mettl14介导的m6A修饰TRPA1通过促进NR2B磷酸化促进宫颈扩张引起的急性内脏痛。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-16 DOI: 10.1016/j.cellsig.2025.111610

Guangfa Xia , Jing Qian , Yu Wang , Fei Xiao

Background

While TRPA1 serves as a therapeutic target for nociceptive pain, its role in acute visceral pain induced by uterine cervical dilation (UCD) remains an enigma. This study aims to elucidate the upstream and downstream mechanisms of TRPA1 in the context of UCD-induced acute visceral pain.

Methods

The UCD rats were administered with SAH (inhibitor of the METTL3-METTL14 complex) via intrathecal tubing. Validate UCD model by measuring spinal c-Fos expression and EMG. The levels of TRPA1 and p-NR2B were evaluated by qRT-PCR and western blot，and m6A level was detected by the kit. RNA Immunoprecipitation was adopted to determine the binding between TRPA1 and METTL14. Neurons were isolated from rat dorsal root ganglia (DRG), exposed to SAH treatment, and subsequently subjected to actinomycin D experiments.

Results

In the UCD model, cervical dilation causes an increase in EMG signal and spinal cord c-Fos expression. At the same time, the levels of TRPA1, p-NR2B, METTL14, and m6A increased in a stimulus intensity-dependent manner. Intrathecal SAH, a METTL3-METTL14 inhibitor, alleviated UCD-induced pain and reversed above indicators. Further investigation revealed that METTL14 binds to TRPA1, increasing TRPA1 mRNA stability via m6A modification.

Conclusion

METTL14 stabilizes TRPA1 through m6A modification, thereby promoting NR2B phosphorylation, culminating in acute visceral pain induced by UCD.

背景：虽然TRPA1是痛觉性疼痛的治疗靶点，但其在宫颈扩张（UCD）引起的急性内脏痛中的作用仍然是一个谜。本研究旨在阐明TRPA1在ucd诱导的急性内脏疼痛中的上下游机制。方法：将METTL3-METTL14复合物抑制剂SAH经鞘内插管给予UCD大鼠。通过测量脊髓c-Fos表达和肌电图验证UCD模型。采用qRT-PCR和western blot检测TRPA1和p-NR2B水平，试剂盒检测m6A水平。采用RNA免疫沉淀法测定TRPA1与METTL14的结合情况。从大鼠背根神经节（DRG）中分离神经元，经SAH处理后进行放线菌素D实验。结果：在UCD模型中，宫颈扩张引起肌电图信号和脊髓c-Fos表达增加。同时，TRPA1、p-NR2B、METTL14、m6A水平呈刺激强度依赖性升高。鞘内SAH是一种METTL3-METTL14抑制剂，可减轻ucd诱导的疼痛，逆转上述指标。进一步研究发现，METTL14与TRPA1结合，通过m6A修饰提高TRPA1 mRNA的稳定性。结论：METTL14通过m6A修饰稳定TRPA1，从而促进NR2B磷酸化，最终导致UCD诱导的急性内脏痛。

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引用次数: 0

Epicatechin protects mice against OVA-induced asthma through inhibiting airway inflammation and modulating gut microbiota 表儿茶素通过抑制气道炎症和调节肠道微生物群来保护小鼠免受ova诱导的哮喘。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-16 DOI: 10.1016/j.cellsig.2025.111609

Yang Zheng , Dengyu Gao , Hongyang Xie , Huafeng Geng

Allergic asthma is a chronic airway inflammatory reaction that seriously affects people's quality of life and even endangers their lives. The aim of this study was to explore the role of epicatechin (EC) on asthma and its potential mechanism. A mice model of allergic asthma was established by intraperitoneal injection of ovalbumin (OVA) with aluminum hydrogen solution, and nebulized inhalation of OVA to stimulate. EC (10, 20, 40 mg/kg) was administered 30 min before nebulization for three consecutive days. The results showed that EC attenuated OVA-induced lung injury, inflammatory cell infiltration, IgE, and inflammatory cytokine production. EC also inhibited OVA-induced NF-κB activation and increased Nrf2 and HO-1 expression. 16S rRNA sequencing analysis demonstrated that at genus level, EC significantly increased the abundance of Lachnospiraceae_NK4A136_group, Ligilactobacillus, Alloprevotella. Meanwhile, EC inhibited the abundance of Clostridia UCG-014, Helicobacter, Paramuribaculum, and Escherichia-Shigella. In conclusion, EC can effectively alleviate the symptoms of asthma in mice, which may through regulating the composition of gut microbiota and inhibiting inflammatory response.

过敏性哮喘是一种慢性气道炎症反应，严重影响人们的生活质量，甚至危及生命。本研究旨在探讨表儿茶素（EC）在哮喘中的作用及其潜在机制。采用氢铝溶液腹腔注射卵清蛋白（OVA），雾化吸入卵清蛋白进行刺激，建立小鼠过敏性哮喘模型。雾化前30 min给药EC(10、20、40 mg/kg)，连续3天。结果表明，EC可减轻ova诱导的肺损伤、炎症细胞浸润、IgE和炎症细胞因子的产生。EC还能抑制ova诱导的NF-κB活化，增加Nrf2和HO-1的表达。16S rRNA测序分析表明，在属水平上，EC显著增加了Lachnospiraceae_NK4A136_group、Ligilactobacillus、Alloprevotella的丰度。同时，EC抑制了Clostridia UCG-014、Helicobacter、paruribaculum和Escherichia-Shigella的丰度。综上所述，EC可有效缓解小鼠哮喘症状，其机制可能与调节肠道菌群组成、抑制炎症反应有关。

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引用次数: 0

Highly expressed VGLL3 in keloid fibroblasts promotes glycolysis and collagen production via the activation of Wnt/β-catenin signaling 在瘢痕疙瘩成纤维细胞中高表达的VGLL3通过激活Wnt/β-catenin信号通路促进糖酵解和胶原生成。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-16 DOI: 10.1016/j.cellsig.2025.111604

Yining Liu , Zelei Yang , Nan Lin , Yanxin Liu , Huaxia Chen

Purpose

This study investigated the effects and related mechanisms of Vestigial-like family member 3 (VGLL3) on keloid fibroblast (KF) proliferation, apoptosis, collagen production, and glycolysis.

Methods

Western blot, qRT-PCR, and immunohistochemistry were used for determining VGLL3 expression. KF viability, proliferation, and apoptosis were assessed using CCK-8 assay, EdU assay, and flow cytometry. Changes in the protein expression levels of α-SMA, fibronectin, collagen I, and collagen III were examined utilizing western blotting. The pathways related to VGLL3 were analyzed using Gene Set Enrichment Analysis. Changes in glycolysis were assessed by measuring oxygen consumption rate (OCR), extracellular acidification rate (ECAR), glucose uptake, and lactate production. WNT2 and β-catenin protein levels were measured using western blotting.

Results

VGLL3 was upregulated in human keloid tissues. In KFs, overexpression of VGLL3 inhibited cell apoptosis, promoted cell proliferation and protein expression of α-SMA, fibronectin, collagen I, and collagen III. Moreover, it reduced OCR level, and increased the levels of ECAR, glucose uptake, and lactate production. On the other hand, the knockdown of VGLL3 had the opposite effect. WNT2 and β-catenin protein levels were enhanced by overexpression of VGLL3 and reduced by VGLL3 knockdown. Silencing of WNT2 reversed the effects of VGLL3 on apoptosis, proliferation, collagen production, and glycolysis in KFs.

Conclusions

VGLL3 promoted glycolysis in KFs and keloid progression, which was achieved through the activation of Wnt signaling pathway. Therefore, targeting VGLL3 may be a promising therapeutic strategy for the treatment of keloids.

目的：研究退化样家族成员3 （VGLL3）对瘢痕疙瘩成纤维细胞（KF）增殖、凋亡、胶原生成和糖酵解的影响及其相关机制。方法：采用Western blot、qRT-PCR、免疫组化检测VGLL3的表达。采用CCK-8法、EdU法和流式细胞术评估KF活力、增殖和凋亡。western blotting检测α-SMA、纤维连接蛋白、I型胶原和III型胶原蛋白表达水平的变化。利用基因集富集分析方法分析与VGLL3相关的途径。通过测量耗氧量（OCR）、细胞外酸化率（ECAR）、葡萄糖摄取和乳酸生成来评估糖酵解的变化。western blotting检测WNT2和β-catenin蛋白水平。结果：VGLL3在瘢痕疙瘩组织中表达上调。在KFs中，过表达VGLL3抑制细胞凋亡，促进细胞增殖和α-SMA、纤维连接蛋白、I型胶原和III型胶原蛋白的表达。此外，它降低了OCR水平，增加了ECAR水平、葡萄糖摄取和乳酸生成。另一方面，VGLL3的敲低则具有相反的效果。过表达VGLL3可提高WNT2和β-catenin蛋白水平，敲低VGLL3可降低WNT2和β-catenin蛋白水平。沉默WNT2逆转了VGLL3对KFs细胞凋亡、增殖、胶原生成和糖酵解的影响。结论：VGLL3促进KFs中的糖酵解和瘢痕疙瘩进展，这是通过激活Wnt信号通路实现的。因此，靶向VGLL3可能是治疗瘢痕疙瘩的一种有前景的治疗策略。

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引用次数: 0

Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention 通过单细胞测序和烯醇干预揭示MDH1在乳腺癌耐药中的作用。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-14 DOI: 10.1016/j.cellsig.2025.111608

Jian Lu , Feng Ding , Yongjie Sun , Yu Zhao , Wenbiao Ma , Huan Zhang , Bo Shi

This study utilizes single-cell RNA sequencing data to reveal the transcriptomic characteristics of breast cancer and normal epithelial cells. Nine significant cell populations were identified through stringent quality control and batch effect correction. Further classification of breast cancer epithelial cells based on the PAM50 method and clinical subtypes highlighted significant heterogeneity between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC). The study also analyzed myeloid cells and tumor-infiltrating lymphocytes (TILs) within the breast cancer immune microenvironment, identifying 14 TIL subpopulations and assessing their proportion variations across different patients. The CellChat tool revealed a complex cellular communication network within the tumor microenvironment, showing notable differences in communication intensity and patterns between TNBC and NTNBC patients. Additionally, the key regulatory role of the senescence-associated gene MDH1 in breast cancer was confirmed, and its impact on drug sensitivity was explored. Finally, it was discovered that the phytosterol Schottenol inhibits breast cancer cell proliferation by downregulating MDH1 expression and enhances sensitivity to paclitaxel. These findings provide new insights into MDH1 as a therapeutic target and suggest Schottenol as a potential strategy to overcome breast cancer drug resistance.

本研究利用单细胞RNA测序数据揭示乳腺癌和正常上皮细胞的转录组学特征。通过严格的质量控制和批量效应校正，鉴定出9个显著的细胞群。基于PAM50方法和临床亚型对乳腺癌上皮细胞的进一步分类表明，三阴性乳腺癌（TNBC）和非三阴性乳腺癌（NTNBC）之间存在显著的异质性。该研究还分析了乳腺癌免疫微环境中的骨髓细胞和肿瘤浸润淋巴细胞（TIL），确定了14个TIL亚群，并评估了它们在不同患者中的比例变化。CellChat工具揭示了肿瘤微环境中复杂的细胞通信网络，显示TNBC和NTNBC患者之间的通信强度和模式存在显著差异。此外，我们还证实了衰老相关基因MDH1在乳腺癌中的关键调控作用，并探讨了其对药物敏感性的影响。最后发现植物甾醇Schottenol通过下调MDH1表达抑制乳腺癌细胞增殖，增强对紫杉醇的敏感性。这些发现为MDH1作为治疗靶点提供了新的见解，并表明Schottenol是克服乳腺癌耐药的潜在策略。

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引用次数: 0

Identification of PLAC1 as a prognostic biomarker and molecular target in clear cell renal cell carcinoma PLAC1作为透明细胞肾细胞癌预后生物标志物和分子靶点的鉴定。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-13 DOI: 10.1016/j.cellsig.2025.111606

Ying Kong , Zongming Jia , Yizhang Sun , Lichen Jin , Tong Zhang , Qiya Xu , Yuhua Huang

Clear cell renal cell carcinoma (ccRCC) is a common clinical tumor of the urinary system. The lack of effective diagnostic and treatment options poses a serious challenge to clinical treatment. Therefore, identifying effective molecular targets has become one of the potential means to treat this disease. Firstly, the analysis of the TCGA database found that PLAC1 was abnormally highly expressed in ccRCC and was negatively correlated with patient prognosis. Western blotting and immunofluorescence experiments further verified that PLAC1 was highly expressed in ccRCC patients, and knockdown of PLAC1 inhibited the development of ccRCC in vitro. Last, high-throughput virtual screening technology (HTVS) was performed to identify two molecular inhibitors ，AmB and Cana, which were able to reduce the expression of PLAC1 and inhibited the progression of ccRCC. In conclusion, the current investigation indicated that the PLAC1 could serve as a prognostic biomarker, and AmB and Cana inhibit the progression of ccRCC by reducing PLAC1, making it a potential therapeutic option for ccRCC.

透明细胞肾细胞癌（ccRCC）是泌尿系统常见的临床肿瘤。缺乏有效的诊断和治疗方案对临床治疗提出了严峻的挑战。因此，寻找有效的分子靶点已成为治疗该病的潜在手段之一。首先，通过TCGA数据库分析发现，PLAC1在ccRCC中异常高表达，且与患者预后呈负相关。Western blotting和免疫荧光实验进一步证实了PLAC1在ccRCC患者中高表达，在体外敲低PLAC1可抑制ccRCC的发展。最后，利用高通量虚拟筛选技术（HTVS）鉴定出两个能够降低PLAC1表达并抑制ccRCC进展的分子抑制剂AmB和Cana。总之，目前的研究表明，PLAC1可以作为一种预后生物标志物，AmB和Cana通过降低PLAC1抑制ccRCC的进展，使其成为ccRCC的潜在治疗选择。

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引用次数: 0

Aquaporin-5 facilitates liver regeneration following hepatectomy via ROS/GSDMD pathway 水通道蛋白-5通过ROS/GSDMD途径促进肝切除术后肝脏再生。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-13 DOI: 10.1016/j.cellsig.2025.111602

Bin Li , Guohu Di , Huanhuan Ge , Peirong Song , Wenshuo Han , Hetong Sun , Dianqiang Wang , Peng Chen , Ye Wang

During the proliferative phase of liver regeneration, insufficient regulation of hepatocyte hydrogen peroxide (H₂O₂) overproduction can result in oxidative stress and hepatocyte death. This study aims to investigate the influence of Aquaporin 5 (Aqp5) on liver regeneration by evaluating its role in reactive oxygen species (ROS) generation and NLRP3-GSDMD-mediated pyroptosis. A 70 % partial hepatectomy (PHx) model was established in Aqp5^−/− mice to evaluate the pathological changes in the liver. Reactive oxygen species (ROS) production was assessed using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Aqp5 deficiency significantly increased ROS production, the number of TUNEL-positive cells, and disrupted mitochondrial membrane potential in the liver of Aqp5-deficient mice. The impact of Aqp5 on ROS/NLRP3/Gasdermin-D (GSDMD)-mediated pyroptosis was examined through the administration of N-acetyl-L-cysteine (NAC, an ROS scavenger) or disulfiram (DSF, a GSDMD inhibitor). In Aqp5-deficient mice, the regenerative liver exhibited increased expression of NLRP3, enhanced activation of caspase-1 and GSDMD, as well as elevated secretion of IL-1β. Treatment with DSF significantly attenuated GSDMD-mediated pyroptosis triggered by Aqp5 deficiency in the regenerating liver. Furthermore, the administration of NAC to Aqp5-deficient mice resulted in a reduction in the expression levels of NLRP3, the activity levels of caspase-1 and GSDMD, as well as the release of IL-1β. Our findings indicate that the deficiency of Aqp5 facilitates GSDMD activation through the production of ROS. The suppression of ROS or inhibition of GSDMD significantly alleviates the damage and pyroptosis observed in Aqp5-deficient regenerative liver.

在肝脏再生的增殖阶段，对肝细胞过氧化氢（H2O2）过量产生的调节不足可导致氧化应激和肝细胞死亡。本研究旨在通过评价水通道蛋白5 （Aquaporin 5, Aqp5）在活性氧（reactive oxygen species， ROS）生成和nlrp3 - gsdmd介导的焦亡中的作用，探讨其对肝脏再生的影响。建立Aqp5-/-小鼠70%部分肝切除（PHx）模型，观察其肝脏病理变化。采用二氯二氢荧光素（DCFH-DA）测定法评估活性氧（ROS）的产生。Aqp5缺乏显著增加了活性氧的产生、tunel阳性细胞的数量以及Aqp5缺乏小鼠肝脏线粒体膜电位的破坏。通过给药n-乙酰- l-半胱氨酸（NAC，一种ROS清除剂）或双硫醚（DSF，一种GSDMD抑制剂）来检测Aqp5对ROS/NLRP3/Gasdermin-D （GSDMD）介导的焦亡的影响。在aqp5缺失小鼠中，再生肝脏表现出NLRP3表达增加，caspase-1和GSDMD激活增强，IL-1β分泌升高。DSF治疗可显著减轻再生肝中Aqp5缺乏引起的gsdmd介导的焦亡。此外，NAC对aqp5缺陷小鼠的处理导致NLRP3表达水平降低，caspase-1和GSDMD活性水平降低，IL-1β释放降低。我们的研究结果表明，Aqp5的缺乏通过ROS的产生促进了GSDMD的激活。抑制ROS或抑制GSDMD可显著减轻aqp5缺失再生肝的损伤和焦亡。

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引用次数: 0

Corrigendum to “The role of α7nAchR and PD-L1 in neuroimmune regulation of keloid treatment” [Cellular Signalling, Volume 121 (2024), Article 111275] “α7nAchR和PD-L1在瘢痕疙瘩治疗的神经免疫调节中的作用”的更正[细胞信号传导，第121卷（2024），第111275条]。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-13 DOI: 10.1016/j.cellsig.2025.111599

Zucheng Luo , Shaoluan Zheng , Jiaqi Liu , Fazhi Qi

引用次数: 0

Corrigendum to “MicroRNA-206 in human cancer: Mechanistic and clinical perspectives” [Cellular Signalling, volume 101, Article 110525] “人类癌症中的MicroRNA-206：机制和临床观点”的勘误表[细胞信号传导，第101卷，第110525条]。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-11 DOI: 10.1016/j.cellsig.2025.111597

Leila Bahari Khasraghi , Morteza Nouri , Masoud Vazirzadeh , Nasrin Hashemipour , Mehrdad Talebi , Fatemehsadat Aghaei Zarch , Jamal Majidpoor , Kambiz Kalhor , Poopak Farnia , Sajad Najafi , Seyed Mohsen Aghaei Zarch

引用次数: 0

Effect of the glucagon-like peptide-1 receptor agonists dulaglutide on kidney outcomes in db/db mice 胰高血糖素样肽-1受体激动剂dulaglutide对db/db小鼠肾脏预后的影响。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-01-11 DOI: 10.1016/j.cellsig.2025.111603

Fengyi Deng , Ping Zhang , Huaiyun Li , Xingyu Fan , Yijun Du , Xing Zhong , Nuojin Wang , Meiwen He , Yue Wang , Tianrong Pan

Diabetic kidney disease (DKD), a microvascular complication of diabetes mellitus, represents a significant clinical challenge. This study investigated the reno-protective effects of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) widely used in the management of diabetes, and aimed to elucidate its underlying mechanisms. Mice with db/db and db/m genotypes were allocated into four experimental groups and treated with either dulaglutide or a saline control for 10 weeks. Following the treatment period, biological samples were collected for comprehensive analysis. Serum and urinary creatinine levels were measured using a creatinine assay, while urinary protein concentrations were quantified via ELISA. Histopathological kidney damage was assessed through hematoxylin and eosin (HE) staining, with glomerular lesions evaluated using periodic acid-Schiff (PAS) staining. Inflammatory markers, ferroptosis-related indicators, and fibrosis in kidney tissues were further analyzed through PCR, Western blot (WB), immunohistochemistry (IHC), and transmission electron microscopy (TEM). Consistent with prior findings, this research demonstrated that dulaglutide improves renal function and mitigates pathological kidney damage in db/db mice. Treatment with dulaglutide significantly reduced mRNA expression of ferroptosis-related markers, including ACSL4, SLC7A11, and Ptgs2, alongside a decrease in 4-HNE levels in kidney tissues. Furthermore, dulaglutide downregulated ACSL4 protein levels and upregulated GPX4 protein expression, thereby ameliorating mitochondrial damage in renal tubular cells. In addition to these effects, dulaglutide alleviated kidney inflammation and fibrosis in db/db mice, with concomitant suppression of P-STAT3 and P-ERK expression. Collectively, these findings underscore dulaglutide's reno-protective effects in DKD, mediated through the inhibition of inflammation, improvement in renal fibrosis and ferroptosis, and modulation of P-STAT3 and P-ERK signaling pathways.

糖尿病肾病（DKD）是糖尿病的微血管并发症，是一个重大的临床挑战。本研究探讨了胰高血糖素样肽-1受体激动剂（GLP-1 RA）在糖尿病治疗中广泛应用的肾保护作用，并旨在阐明其潜在机制。将db/db和db/m基因型小鼠分为4个实验组，分别给予杜拉鲁肽或生理盐水对照治疗10 周。治疗期结束后，采集生物样本进行综合分析。采用肌酐测定法测定血清和尿肌酐水平，通过ELISA测定尿蛋白浓度。组织病理学肾损害通过苏木精和伊红（HE）染色评估，肾小球病变采用周期性酸-希夫（PAS）染色评估。通过PCR、Western blot （WB）、免疫组化（IHC）、透射电镜（TEM）等方法进一步分析肾脏组织的炎症标志物、凋亡相关指标及纤维化情况。与先前的研究结果一致，本研究表明杜拉鲁肽可以改善db/db小鼠的肾功能并减轻病理性肾损伤。杜拉鲁肽治疗显著降低了铁中毒相关标志物的mRNA表达，包括ACSL4、SLC7A11和Ptgs2，同时降低了肾组织中4-HNE的水平。此外，杜拉鲁肽下调ACSL4蛋白水平，上调GPX4蛋白表达，从而改善肾小管细胞线粒体损伤。除了这些作用外，杜拉鲁肽还能减轻db/db小鼠的肾脏炎症和纤维化，同时抑制P-STAT3和P-ERK的表达。总的来说，这些发现强调了杜拉鲁肽在DKD中的肾保护作用，通过抑制炎症、改善肾纤维化和铁下垂以及调节P-STAT3和P-ERK信号通路来介导。

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引用次数: 0