Sp1-like protein KLF13 acts as a negative feedback regulator of TGF-(3 signaling and fibrosis

Yang, Shu1,2,3,8,9; Xiang, Jiaqing1,8,9; Ma, Chuanrui4,5; Yang, Guangyan1,2,3,8,9; Wang, Xinyu1,8,9; Liu, Hanyong6,8,9; Fan, Guanwei4,5; Kang, Lin1,2,3,7,8,9; Liang, Zhen1,2,3,8,9

2023-04-25

10.1016/j.celrep.2023.112367

CELL REPORTS   影响因子和分区

2211-1247

Transforming growth factor (3 (TGF-(3) 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-(3 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-(3 target genes, limiting the profi-brotic effects of TGF-(3. Temporary upregulation of TGF-(3 induces KLF13 expression, creating a negative feedback loop that triggers the anti-fibrotic effect of KLF13. However, persistent activation of TGF-(3 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-(3 signaling and fibrosis.

SCI

英语

第一 ; 通讯

National Natural Science Founda- tion of China, China["82000824","82003747","82170842","82171556"] ; National Natural Science Foundation of China["82000824","82003747","82170842","82171556"] ; Natural Science Foundation of Shenzhen City, China[KCXFZ20201221173600001] ; National Key Research and Development Program of China[2018YFC2001100] ; Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine, China["ZYYCXTD-C-202203","ZYYCXTD-D-202207"]

Cell Biology

Cell Biology

WOS:000980711000001

CELL PRESS

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Geriatr, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
2.Jinan Univ, Shenzhen Peoples Hosp, Guangdong Prov Clin Res Ctr Geriatr, Shenzhen Clin Res Ctr Geriatr,Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
4.Tianjin Univ Tradit Chinese Med, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, Teaching Hosp 1, Tianjin 300381, Peoples R China
5.Haihe Lab Modern Chinese Med, Tianjin 301617, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Nephrol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
7.Shenzhen Peoples Hosp, Biobank Natl Innovat Ctr Adv Med Devices, Shenzhen 518020, Guangdong, Peoples R China
8.Jinan Univ, Shenzhen Peoples Hosp, Guangdong Prov Clin Res Ctr Geriatr, Shenzhen Clin Res Ctr Geriatr,Clin Med Coll 2, Shenzhen, Guangdong, Peoples R China
9.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China

Yang, Shu,Xiang, Jiaqing,Ma, Chuanrui,et al. Sp1-like protein KLF13 acts as a negative feedback regulator of TGF-(3 signaling and fibrosis[J]. CELL REPORTS,2023,42(4).

Yang, Shu.,Xiang, Jiaqing.,Ma, Chuanrui.,Yang, Guangyan.,Wang, Xinyu.,...&Liang, Zhen.(2023).Sp1-like protein KLF13 acts as a negative feedback regulator of TGF-(3 signaling and fibrosis.CELL REPORTS,42(4).

Yang, Shu,et al."Sp1-like protein KLF13 acts as a negative feedback regulator of TGF-(3 signaling and fibrosis".CELL REPORTS 42.4(2023).