| First Author | Xiao CC | Year | 2017 |
| Journal | Cell Physiol Biochem | Volume | 42 |
| Issue | 2 | Pages | 697-712 |
| PubMed ID | 28618421 | Mgi Jnum | J:334707 |
| Mgi Id | MGI:6834359 | Doi | 10.1159/000477887 |
| Citation | Xiao CC, et al. (2017) Identification of Tisp40 as an Essential Regulator of Renal Tubulointerstitial Fibrosis via TGF-beta/Smads Pathway. Cell Physiol Biochem 42(2):697-712 |
| abstractText | BACKGROUND: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. METHODS: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT) and the underlying molecular mechanisms in transforming growth factor-beta (TGF-beta)-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R) by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo. RESULTS: The data showed that Tisp40 was upregulated in a model of renal fibrosis induced by I/R injury (IRI). Upon IRI, Tisp40-deficient mice showed attenuated renal fibrosis compared with wild-type mice. Furthermore, the expression of alpha-smooth muscle actin, E-cadherin, fibronectin, and collagen I was suppressed. Tisp40 overexpression aggravated ECM accumulation and EMT in the TGF-beta-stimulated TCMK-1 cell line, whereas the opposite occurred in cells treated with small interfering RNA (siRNA) targeting Tisp40. Importantly, it is changes in the Smad pathway that attenuate renal fibrosis. CONCLUSION: These findings suggest that Tisp40 plays a critical role in the TGF-beta/ Smads pathway involved in this process. Hence, Tisp40 could be a useful therapeutic target in the fight against renal tubulointerstitial fibrosis. |
