PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury

doi:10.1038/srep39888

	PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury
	Yang, Bo 1; Chen, Sixiu 1; Wu, Ming 1; Zhang, Lin 2; Ruan, Mengna 1; Chen, Xujiao 1; Chen, Zhengjun2,3 ; Mei, Changlin 1; Mao, Zhiguo 1
	2017-01-03
发表期刊	SCIENTIFIC REPORTS (IF:3.8[JCR-2023],4.3[5-Year])
ISSN	2045-2322
卷号	7
发表状态	已发表
DOI	10.1038/srep39888
摘要	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 wildtype 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.
收录类别	SCI
语种	英语
资助项目	Key Projects in the National Science & Technology Pillar Program in the Twelfth Five-year Plan Period[2011BAI10B00]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000391167100001
出版者	NATURE PUBLISHING GROUP
WOS关键词	TGF-BETA ; GROWTH-FACTOR ; TUBULOINTERSTITIAL FIBROSIS ; MOLECULAR-MECHANISMS ; DISEASE ; FAILURE ; GENE ; PDGF ; ACTIVATION ; REGULATOR
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1556
专题	生命科学与技术学院_特聘教授组_陈正军组
通讯作者	Chen, Zhengjun; Mei, Changlin; Mao, Zhiguo
作者单位	1.Second Mil Med Univ, Changzheng Hosp, Div Nephrol, Kidney Inst CPLA, Shanghai 200003, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yang, Bo,Chen, Sixiu,Wu, Ming,et al. PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury[J]. SCIENTIFIC REPORTS,2017,7.
APA	Yang, Bo.,Chen, Sixiu.,Wu, Ming.,Zhang, Lin.,Ruan, Mengna.,...&Mao, Zhiguo.(2017).PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury.SCIENTIFIC REPORTS,7.
MLA	Yang, Bo,et al."PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury".SCIENTIFIC REPORTS 7(2017).