2. Academic Validation
  3. Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis

Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis

  • Cell Death Dis. 2023 Aug 29;14(8):571. doi: 10.1038/s41419-023-06093-4.
Yang Du 1 2 3,  Yaqiong Shang 1 2,  Yun Qian 1 2,  Yan Guo 1 2 3,  Shuang Chen 1 2 3,  Xiuli Lin 1 2,  Weidong Cao 1 2 3,  Xiaomei Tang 1 2,  Anning Zhou 1 2,  Songming Huang 1 2 3,  Aihua Zhang 4 5 6,  Zhanjun Jia 7 8 9,  Yue Zhang 10 11 12
Affiliations

Affiliations

  • 1 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Gulou District, 210008, Nanjing, China.
  • 2 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Hanzhong Road #140, Gulou District, 210029, Nanjing, China.
  • 3 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Gulou District, Guangzhou Road #72, 210008, Nanjing, China.
  • 4 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Gulou District, 210008, Nanjing, China. zhaihua@njmu.edu.cn.
  • 5 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Hanzhong Road #140, Gulou District, 210029, Nanjing, China. zhaihua@njmu.edu.cn.
  • 6 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Gulou District, Guangzhou Road #72, 210008, Nanjing, China. zhaihua@njmu.edu.cn.
  • 7 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Gulou District, 210008, Nanjing, China. jiazj72@hotmail.com.
  • 8 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Hanzhong Road #140, Gulou District, 210029, Nanjing, China. jiazj72@hotmail.com.
  • 9 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Gulou District, Guangzhou Road #72, 210008, Nanjing, China. jiazj72@hotmail.com.
  • 10 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Gulou District, 210008, Nanjing, China. zyflora2006@hotmail.com.
  • 11 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Hanzhong Road #140, Gulou District, 210029, Nanjing, China. zyflora2006@hotmail.com.
  • 12 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Gulou District, Guangzhou Road #72, 210008, Nanjing, China. zyflora2006@hotmail.com.
PMID: 37640723 DOI: 10.1038/s41419-023-06093-4
Abstract

The prevalence of chronic kidney disease (CKD) has been increasing over the past decades. However, no effective therapies are available for delaying or curing CKD. Progressive fibrosis is the major pathological feature of CKD, which leads to end-stage renal disease (ESRD). The present study showed that Polo-like kinase 1 (PLK1) was upregulated in the kidneys of CKD patients and mice subjected to unilateral ureteral obstruction (UUO) with location in proximal tubules and tubulointerstitial fibroblasts. Pharmacological inhibition, genetic silencing or knockout of PLK1 attenuated obstructive nephropathy due to suppressed fibroblast activation mediated by reduced autophagic flux. We found PLK1 plays a critical role in maintaining intralysosomal pH by regulating ATP6V1A phosphorylation, and inhibition of PLK1 impaired lysosomal function leading to blockade of autophagic flux. In addition, PLK1 also prevented partial epithelial-mesenchymal transition (pEMT) of tubular epithelial cells via Autophagy pathway. In conclusion, this study demonstrated that PLK1 plays a pathogenic role in renal tubulointerstitial fibrosis by regulating Autophagy/lysosome axis. Thus, targeting PLK1 could be a promising strategy for CKD treatment.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z