A new LKB1 activator, piericidin analogue S14, retards renal fibrosis through promoting autophagy and mitochondrial homeostasis in renal tubular epithelial cells.

ABSTRACT: Background: Liver kinase B1 (LKB1) is the key regulator of energy metabolism and cell homeostasis. LKB1 dysfunction plays a key role in renal fibrosis. However, LKB1 activators are scarce in commercial nowadays. This study aims to discover a new drug molecule, piericidin analogue S14 (PA-S14), preventing renal fibrosis as a novel activator to LKB1. Methods: Our group isolated PA-S14 from the broth culture of a marine-derived Streptomyces strain and identified its binding site. We adopted various CKD models or AKI-CKD model (5/6 nephrectomy, UUO, UIRI and adriamycin nephropathy models). TGF-β-stimulated renal tubular cell culture was also tested. Results: We identified that PA-S14 binds with residue D176 in the kinase domain of LKB1, and then induces the activation of L

SUBMITTER: Liu C 

PROVIDER: S-EPMC9576617 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature