| First Author | Yang B | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 39888 | PubMed ID | 28045076 |
| Mgi Jnum | J:276107 | Mgi Id | MGI:6296292 |
| Doi | 10.1038/srep39888 | Citation | Yang B, et al. (2017) PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury. Sci Rep 7:39888 |
| abstractText | PHF14 is a newly identified regulator of mesenchyme growth in embryonic tissues. Previous studies have shown that phf14-null mutants die just after birth due to interstitial tissue hyperplasia in major organs, including the kidneys. The aim of this study was to investigate PHF14 function in renal fibrosis. By studying the chronic kidney injury mouse model, we found that PHF14 was upregulated in fibrotic kidneys after renal insults induced by folic acid administration. Compared with wild-type mice, PHF14-null mice showed more severe renal fibrosis after pro-fibrotic stimuli. Moreover, PHF14 in rat renal fibroblasts was upregulated by transforming growth factor-beta (TGF-beta) stimulation; while this upregulation was inhibited when smad3 phosphorylation was blocked. A chromatin immunoprecipitation (ChIP) assay further indicated that phospho-smad3 (p-smad3) acted as a transcription factor to enhance PHF14 expression. A lack of PHF14 expression enhanced collagen I and alpha-smooth muscle actin (alpha-SMA) synthesis induced by TGF-beta in vitro. PHF14 was involved in inhibition of platelet-derived growth factor (PDGF) signaling overactivation by selectively repressing PDGF receptor-alpha (PDGFR-alpha) transcription. In summary, PHF14 expression was upregulated in fibrotic models in vivo and in vitro, and the TGF-beta/smad3/PHF14 pathway acted as a self-limiting mechanism in the TGF-beta-dominated renal pro-fibrotic process by suppressing PDGFR-alpha expression. |
