LAPTM5 Promotes Age-Related Renal Fibrosis via USP10/PTEN-Mediated Autophagy Inhibition.

Yan Wang, Qian Gu, Xueqi Chen, Xiaowei Yang, Jiajia Zhai, Meizi Kang, Jianqing Wu, Weihong Zhao

Division of Nephrology, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.Division of Nephrology, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. · pubmed

Paper

Abstract

Aging accelerates renal fibrosis driven by renal tubular epithelial cells (RTECs) senescence. However, the underlying molecular mechanisms remain elusive. We demonstrate that lysosomal transmembrane protein 5 (LAPTM5) is markedly upregulated in aged kidney models and correlates with renal senescence and fibrosis severity. Mechanistically, LAPTM5 drives RTECs epithelial-mesenchymal transition (EMT) by interacting with USP10 and facilitating its lysosomal degradation, thereby relieving PTEN-mediated inhibition of the PI3K/AKT/mTOR-mediated autophagy pathway. This accelerates kidney fibrosis. Functionally, PTEN overexpression rescues LAPTM5-induced EMT in RTECs, while the PTEN agonist sophocarpine ameliorates renal fibrosis and preserves function in D-galactose-induced progeroid mice by restoring autophagy. Our findings identify the LAPTM5-USP10-PTEN axis as a critical regulator of autophagy-mediated renal fibrosis in aging kidney.

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Research summary

LAPTM5 promotes renal fibrosis through the USP10/PTEN-mediated inhibition of autophagy in aging kidneys. This paper is relevant as it investigates a molecular mechanism underlying age-related renal fibrosis, which is a significant aspect of aging and its associated diseases.

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