CCN5 Drives Leydig Cell Aging and Testicular Dysfunction: Insights into Fibrosis, Lipid Dysregulation, and Therapeutic Potential.

ABSTRACT: Leydig cells' (LCs') senescence is an important reason for the decline of testicular function in elderly men. Cellular communication network factor 5 (CCN5) regulates lipid metabolism and cellular fibrosis through multiple mechanisms. However, its role in LCs' aging and the underlying molecular mechanisms remain unclear. This study aimed to elucidate the effects and molecular mechanisms by which CCN5 drives aging phenotypes in LCs and to evaluate the potential of targeting CCN5 as a therapeutic strategy for testicular aging. CCN5 expression was located in LCs and elevated in aged testis. Overexpression of CCN5 led to LCs' aging and testis dysfunction. Extracellularly, CCN5 activated β-catenin and SMAD2/3 phosphorylation, promoting the expression of fibrosis-related genes. Intracellularly,

SUBMITTER: Tan X 

PROVIDER: S-EPMC12314281 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature