Inhibition of fibroblast growth factor-inducible 14 attenuates experimental tubulointerstitial fibrosis and profibrotic factor expression of proximal tubular epithelial cells
| العنوان: | Inhibition of fibroblast growth factor-inducible 14 attenuates experimental tubulointerstitial fibrosis and profibrotic factor expression of proximal tubular epithelial cells |
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| المؤلفون: | Yumin Xia, Hanjiang Gu, Mai Luo, Kun-Yi Wu, Mengmeng Liu, Wen Zhang, Xiao Cui, Wei Liu, Ke Li, Huixia Wang, Siyue Zhai |
| المصدر: | Inflammation Research. 70:553-568 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Immunology, Fibroblast growth factor, Collagen Type I, Cell Line, Proinflammatory cytokine, Kidney Tubules, Proximal, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, medicine, Renal fibrosis, Animals, Humans, Receptor, Notch1, Fibroblast, Mice, Knockout, Pharmacology, Mice, Inbred BALB C, biology, Chemistry, Connective Tissue Growth Factor, Cytokine TWEAK, Epithelial Cells, Fibrosis, Actins, Recombinant Proteins, Fibronectins, Fibroblast Growth Factors, Fibronectin, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, Tubulointerstitial fibrosis, Cancer research, Cytokines, Tumor necrosis factor alpha, Jagged-1 Protein, Ureteral Obstruction |
| الوصف: | As a proinflammatory cytokine, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in the progression of renal fibrosis by binding to its receptor, fibroblast growth factor-inducible 14 (Fn14). However, the effect of Fn14 inhibition on tubular epithelial cell-mediated tubulointerstitial fibrosis remains unclear. This study aimed to elucidate the role of TWEAK/Fn14 interaction in the development of experimental tubulointerstitial fibrosis as well as the protective effect of Fn14 knockdown on proximal tubular epithelial cells. A murine model of unilateral ureteral obstruction was constructed in both wild-type and Fn14-deficient BALB/c mice, followed by observation of the tubulointerstitial pathologies. Fn14 deficiency ameliorated the pathological changes, including inflammatory cell infiltration and cell proliferation, accompanied by reduced production of profibrotic factors and extracellular matrix deposition. In vitro experiments showed that TWEAK dose-dependently enhanced the expression of collagen I, fibronectin, and α-smooth muscle actin in proximal tubular epithelial cells. Interestingly, TWEAK also upregulated the expression levels of Notch1/Jagged1. Fn14 knockdown and Notch1/Jagged1 inhibition also mitigated the effect of TWEAK on these cells. In conclusion, TWEAK/Fn14 signals contributed to tubulointerstitial fibrosis by acting on proximal tubular epithelial cells. Fn14 inhibition might be a therapeutic strategy for protecting against renal interstitial fibrosis. |
| تدمد: | 1420-908X 1023-3830 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efa0faa8f856d46938a7b8a2fefb37f5 https://doi.org/10.1007/s00011-021-01455-0 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....efa0faa8f856d46938a7b8a2fefb37f5 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1420908X 10233830 |
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