Cell Signal. 2026 Jan 9:112359. doi: 10.1016/j.cellsig.2026.112359. Online ahead of print.
ABSTRACT
Renal fibrosis is a primary pathological feature of chronic kidney disease, with a current lack of effective treatments. In this study, we observed that Limb-bud and Heart (LBH) expression was upregulated in kidney specimens obtained from patients with chronic kidney disease. During UUO-induced renal fibrosis, both the protein level and mRNA level of LBH were significantly elevated. Furthermore, knockdown of the mouse LBH gene significantly ameliorated renal fibrosis. The application of inhibitors, agonists, and knockout mouse models uniformly verified the role of LBH in alleviating both endoplasmic reticulum stress (ERS) and pyroptosis. Although renal tubular epithelial cells (RTECs) are conventionally considered the initial responders to renal fibrosis, the role and mechanism of LBH in these cells during disease progression remain unclear. Therefore, this study focused on investigating LBH's effects in damaged RTECs. Mechanistic studies demonstrated that within renal tubular epithelial cells, LBH significantly attenuates renal fibrosis by forming a positive feedback loop with TGFβ1 and ERS. This activated ERS subsequently further induces pyroptosis and partial epithelial-mesenchymal transition (pEMT), thereby promoting renal fibrosis. Importantly, LBH deficiency was shown to significantly attenuate renal fibrosis. These collective findings strongly suggest that LBH may constitute a promising therapeutic target for the treatment of renal fibrosis.
PMID:41520745 | DOI:10.1016/j.cellsig.2026.112359