Tubular insulin-induced gene 1 deficiency promotes NAD⁺ consumption and exacerbates kidney fibrosis.

ABSTRACT: Profibrotic proximal tubules (PT) were identified as a unique phenotype of proximal tubule cells (PTCs) in renal fibrosis by single-cell RNA sequencing (scRNA-seq). Controlling the process of renal fibrosis requires understanding how to manage the S1 subset's branch to the S3 subset rather than to the profibrotic PT subset. Insulin-induced gene 1 (Insig1) is one of the branch-dependent genes involved in controlling this process, although its role in renal fibrosis is unknown. Here, we discovered that tubular Insig1 deficiency, rather than fibroblast Insig1 deficiency, plays a detrimental role in the pathogenesis of renal fibrosis in vivo and in vitro. Overexpression of Insig1 profoundly inhibited renal fibrosis. Mechanistically, Insig1 deletion in PTCs boosted SREBP1 nuclear localization,

SUBMITTER: Li S 

PROVIDER: S-EPMC11251182 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature