| First Author | Yang S | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 4 | Pages | 112367 |
| PubMed ID | 37029927 | Mgi Jnum | J:335225 |
| Mgi Id | MGI:7468528 | Doi | 10.1016/j.celrep.2023.112367 |
| Citation | Yang S, et al. (2023) Sp1-like protein KLF13 acts as a negative feedback regulator of TGF-beta signaling and fibrosis. Cell Rep 42(4):112367 |
| abstractText | Transforming growth factor beta (TGF-beta) is the primary factor that drives fibrosis in most forms of chronic kidney disease. The aim of this study was to identify endogenous regulators of TGF-beta signaling and fibrosis. Here, we show that tubulointerstitial fibrosis is aggravated by global deletion of KLF13 and attenuated by adeno-associated virus-mediated KLF13 overexpression in renal tubular epithelial cells. KLF13 recruits a repressor complex comprising SIN3A and histone deacetylase 1 (HDAC1) to the TGF-beta target genes, limiting the profibrotic effects of TGF-beta. Temporary upregulation of TGF-beta induces KLF13 expression, creating a negative feedback loop that triggers the anti-fibrotic effect of KLF13. However, persistent activation of TGF-beta signaling reduces KLF13 levels through FBXW7-mediated ubiquitination degradation and HDAC-dependent mechanisms to inhibit KLF13 transcription and offset the anti-fibrotic effect of KLF13. Collectively, our data demonstrate a role of KLF13 in regulating TGF-beta signaling and fibrosis. |
