Meis1 Targets Protein Tyrosine Phosphatase Receptor J in Fibroblast to Retard Chronic Kidney Disease Progression.

Autor: Bai M; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China.; Nanjing Key Lab of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China., Xu S; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., Jiang M; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., Guo Y; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., Hu D; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., He J; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., Wang T; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., Zhang Y; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China.; Medical School of Nanjing University, Nanjing, 210093, China., Guo Y; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China., Zhang Y; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China.; Nanjing Key Lab of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China., Huang S; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China.; Nanjing Key Lab of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China., Jia Z; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China.; Nanjing Key Lab of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China., Zhang A; Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, 210029, China.; Nanjing Key Lab of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Oct; Vol. 11 (39), pp. e2309754. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1002/advs.202309754
Abstrakt: Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with the proliferation and activation of myofibroblasts being definite effectors and drivers. Here, increased expression of Meis1 (myeloid ecotropic viral integration site 1) is observed, predominantly in the nucleus of the kidney of CKD patients and mice, and negatively correlates with serum creatinine. Fibroblast-specific knock-in of Meis1 inhibits myofibroblast activation and attenuates renal fibrosis and kidney dysfunction in CKD models. Overexpression of Meis1 in NRK-49F cells suppresses the pro-fibrotic response induced by transforming growth factor-β1 but accelerates by its knockdown. Mechanistically, Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis by inhibiting the proliferation and activation of fibroblasts. Finally, a new activator of Ptprj is identified through computer-aided virtual screening, which has the effect of alleviating renal fibrosis. Collectively, these results illustrate that the Meis1/Ptprj axis has therapeutic potential for clinically treating CKD.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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