TY - JOUR
T1 - A negative feedback loop between JNK-associated leucine zipper protein and TGF-β1 regulates kidney fibrosis
AU - Yan, Qi
AU - Zhu, Kai
AU - Zhang, Lu
AU - Fu, Qiang
AU - Chen, Zhaowei
AU - Liu, Shan
AU - Fu, Dou
AU - Nakazato, Ryota
AU - Yoshioka, Katsuji
AU - Diao, Bo
AU - Ding, Guohua
AU - Li, Xiaogang
AU - Wang, Huiming
N1 - Funding Information:
This work was supported by the grants from the National Natural Science Foundation of China (#81172793 and #81370800 to Dr. Huiming Wang, #81800603 to Dr. Qi Yan and #81800614 to Dr. Lu Zhang), the Key Project on Science and Technology Innovation of Hubei Province (#2019ACA137 to Dr. Huiming Wang). This study is also supported by National Institutes of Health (NIH) grant R01 DK084097 to Dr. Xiaogang Li.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Renal fibrosis is controlled by profibrotic and antifibrotic forces. Exploring anti-fibrosis factors and mechanisms is an attractive strategy to prevent organ failure. Here we identified the JNK-associated leucine zipper protein (JLP) as a potential endogenous antifibrotic factor. JLP, predominantly expressed in renal tubular epithelial cells (TECs) in normal human or mouse kidneys, was downregulated in fibrotic kidneys. Jlp deficiency resulted in more severe renal fibrosis in unilateral ureteral obstruction (UUO) mice, while renal fibrosis resistance was observed in TECs-specific transgenic Jlp mice. JLP executes its protective role in renal fibrosis via negatively regulating TGF-β1 expression and autophagy, and the profibrotic effects of ECM production, epithelial-to-mesenchymal transition (EMT), apoptosis and cell cycle arrest in TECs. We further found that TGF-β1 and FGF-2 could negatively regulate the expression of JLP. Our study suggests that JLP plays a central role in renal fibrosis via its negative crosstalk with the profibrotic factor, TGF-β1.
AB - Renal fibrosis is controlled by profibrotic and antifibrotic forces. Exploring anti-fibrosis factors and mechanisms is an attractive strategy to prevent organ failure. Here we identified the JNK-associated leucine zipper protein (JLP) as a potential endogenous antifibrotic factor. JLP, predominantly expressed in renal tubular epithelial cells (TECs) in normal human or mouse kidneys, was downregulated in fibrotic kidneys. Jlp deficiency resulted in more severe renal fibrosis in unilateral ureteral obstruction (UUO) mice, while renal fibrosis resistance was observed in TECs-specific transgenic Jlp mice. JLP executes its protective role in renal fibrosis via negatively regulating TGF-β1 expression and autophagy, and the profibrotic effects of ECM production, epithelial-to-mesenchymal transition (EMT), apoptosis and cell cycle arrest in TECs. We further found that TGF-β1 and FGF-2 could negatively regulate the expression of JLP. Our study suggests that JLP plays a central role in renal fibrosis via its negative crosstalk with the profibrotic factor, TGF-β1.
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U2 - 10.1038/s42003-020-1008-z
DO - 10.1038/s42003-020-1008-z
M3 - Article
C2 - 32504044
AN - SCOPUS:85085988356
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 288
ER -