title: PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury.
abstract: 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-β (TGF-β) 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 α-smooth muscle actin (α-SMA) synthesis induced by TGF-β in vitro. PHF14 was involved in inhibition of platelet-derived growth factor (PDGF) signaling overactivation by selectively repressing PDGF receptor-α (PDGFR-α) transcription. In summary, PHF14 expression was upregulated in fibrotic models in vivo and in vitro, and the TGF-β/smad3/PHF14 pathway acted as a self-limiting mechanism in the TGF-β-dominated renal pro-fibrotic process by suppressing PDGFR-α expression.
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Sixiu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Mengna
authors.initials: M
authors.lastname: Ruan
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Xujiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, People's Republic of China.|State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.affiliation: Kidney Institute of CPLA, Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Mao
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D005492:Folic Acid / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000199:Actins; D024042:Collagen Type I; C576054:Phf14 protein, mouse; D010982:Platelet-Derived Growth Factor; D051900:Smad3 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D005492:Folic Acid; D020796:Receptor, Platelet-Derived Growth Factor alpha