Academic Journal
Transient receptor potential canonical 6 knockdown ameliorated diabetic kidney disease by inhibiting nuclear factor of activated T cells 2 expression in glomerular mesangial cells
| العنوان: | Transient receptor potential canonical 6 knockdown ameliorated diabetic kidney disease by inhibiting nuclear factor of activated T cells 2 expression in glomerular mesangial cells |
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| المؤلفون: | Jian Yu, Chunchun Li, Lisha Ma, Bin Zhai, Aiping Xu, Decui Shao |
| المصدر: | Renal Failure, Vol 44, Iss 1, Pp 1780-1790 (2022) |
| بيانات النشر: | Taylor & Francis Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Diseases of the genitourinary system. Urology |
| مصطلحات موضوعية: | Diabetic kidney disease, glomerular mesangial cells, TRPC6, NFAT2, high glucose, extracellular matrix, Diseases of the genitourinary system. Urology, RC870-923 |
| الوصف: | Purpose Glomerular mesangial cell (GMC) dysfunction plays a vital role in the pathogenesis of diabetic kidney disease (DKD). Transient receptor potential canonical 6 (TRPC6) has been demonstrated to be involved in the development of DKD. However, the underlying mechanism remains unclear. The present study investigated the role of TRPC6 in GMC dysfunction and the related mechanism.Methods Diabetic rats and cultured GMCs were used in the experiment. The diabetic rat model was created by intraperitoneal injection of streptozotocin. Protein and mRNA levels were assessed by Western blotting and quantitative RT–PCR, respectively. Histological changes in the kidneys were observed by immunochemistry and hematoxylin and eosin. TRPC6 knockdown was achieved by adenovirus-mediated TRPC6 shRNA delivery in vivo and TRPC6 siRNA transfection in vitro.Results TRPC6 expression was increased in diabetic rat kidneys. Knockdown of TRPC6 attenuated diabetes-induced kidney functional deterioration. In addition, the increases in extracellular matrix components, including collagen IV, collagen I, and fibronectin production, as well as NFAT2 expression were also suppressed. In cultured GMCs, high glucose (25 mM, HG) treatment increased the expression of TRPC6. Knockdown of TRPC6 alleviated HG-induced increases in collagen IV, fibronectin, and NFAT2 expression. Knockdown of NFAT2 also inhibited the upregulation of proteins, including collagen IV and fibronectin, in HG-treated GMCs.Conclusion These results demonstrate that inhibition of TRPC6/NFAT2 signaling attenuates GMC dysfunction and the development of DKD and suggest that pharmacological targeting of TRPC6/NFAT2 in GMCs may provide beneficial effects for DKD. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0886022X 1525-6049 0886-022X 83637346 |
| Relation: | https://doaj.org/toc/0886-022X; https://doaj.org/toc/1525-6049 |
| DOI: | 10.1080/0886022X.2022.2134796 |
| URL الوصول: | https://doaj.org/article/5790725f73cd47ecb83637346b489078 |
| رقم الانضمام: | edsdoj.5790725f73cd47ecb83637346b489078 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 0886022X 15256049 83637346 |
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| DOI: | 10.1080/0886022X.2022.2134796 |