Project description:AMP-activated protein kinase (AMPK) stabilizes tubular cell metabolism and protects against renal fibrosis through promoting autophagy and mitochondrial homeostasis. Liver kinase B1 (LKB1) is the key regulator for AMPK activation. However, the direct activators of LKB1 are scarce in commercial. In this study, we report a novel LKB1 activator, the piericidin analogue S14 (PA-S14), which was isolated from the culture broth of a marine-derived Streptomyces strain by our group. PA-S14 binds with residue D176 in LKB1 kinase domain, and then induces LKB1 phosphorylated activation and its complex formation with MO25 and STRADα. Furthermore, PA-S14 promotes AMPK activation to enhance LC3B-II/LC3B-I ratio, trigger autophagosome formation and increase autophagic flux. PA-S14 exhibits perfect protective effects on stabilizing mitochondrial homeostasis, inhibiting tubular cell senescence, and retarding fibrogenesis in various CKD models (UUO, UIRI and adriamycin nephropathy models) and TGF-β-stimulated tubular cell culture. Transcriptomics sequencing and site-specific mutation analysis further prove that PA-S14 is a novel lead compound of LKB1 activator, which perfectly protects against renal fibrosis through inducing AMPK-mediated autophagy and mitochondrial homeostasis.

2022-10-26 | GSE193072 | GEO

A new LKB1 activator, Piericidin Analogue S14, attenuates tubular cell senescence and renal fibrosis through promoting AMPK-induced autophagy and mitochondrial homeostasis pathway [I]

2022-10-26 | GSE193067 | GEO

Methylovulum psychrotolerans strain:HV10_M2

Project description:Methylovulum psychrotolerans strain:HV10_M2 Genome sequencing

| PRJNA391059 | ENA