Activating the Osteoblastic USP26 Pathway Alleviates Multi-Organ Fibrosis by Decreasing Insulin Resistance.

ABSTRACT: Osteoblast dysfunction contributes to systemic metabolic disorders by inducing insulin resistance (IR), a key factor in metabolic-related fibrosis. Therefore, the axis of osteoblast dysfunction, IR, and multi-organ fibrosis represents a crucial pathological pathway. This study revealed that the deletion of Ubiquitin Specific Peptidase 26 (USP26) in osteoblasts leads to decreased bone formation along with multi-organ fibrosis associated with IR. Mechanistically, the loss of USP26 decreases histone H3 lysine 18 lactylation (H3K18LA) in the promoter region of KH-Type Splicing Regulatory Protein (KSRP), resulting in decreased expression of KSRP and decreased alternative splicing of follistatin-like protein 1 (FSTL1) mRNA by KSRP. Elevated FSTL1 expression causes IR and high blood glucose level

SUBMITTER: Tang J 

PROVIDER: S-EPMC12915124 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature