EPRS1-mediated fibroblast activation and mitochondrial dysfunction promote kidney fibrosis.

ABSTRACT: Kidney fibrosis causes irreversible structural damage in chronic kidney disease and is characterized by aberrant extracellular matrix (ECM) accumulation. Although glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is a crucial enzyme involved in proline-rich protein synthesis, its role in kidney fibrosis remains unclear. The present study revealed that EPRS1 expression levels were increased in the fibrotic kidneys of patients and mice, especially in fibroblasts and proximal tubular epithelial cells, on the basis of single-cell analysis and immunostaining of fibrotic kidneys. Moreover, C57BL/6 EPRS1^tm1b heterozygous knockout (Eprs1^+/-) and pharmacological EPRS1 inhibition with the first-in-class EPRS1 inhibitor DWN12088 protected against kidney fibrosis and dysfunction by preve

SUBMITTER: Son SS 

PROVIDER: S-EPMC11671583 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature