Clusterin negatively modulates mechanical stress-mediated ligamentum flavum hypertrophy through TGF-β1 signaling.

ABSTRACT: Ligamentum flavum hypertrophy (LFH) is a major cause of lumbar spinal canal stenosis (LSCS). The pathomechanisms for LFH have not been fully elucidated. Isobaric tags for relative and absolute quantitation (iTRAQ) technology, proteomics assessments of human ligamentum flavum (LF), and successive assays were performed to explore the effect of clusterin (CLU) upregulation on LFH pathogenesis. LFH samples exhibited higher cell positive rates of the CLU, TGF-β1, α-SMA, ALK5 and p-SMAD3 proteins than non-LFH samples. Mechanical stress and TGF-β1 initiated CLU expression in LF cells. Notably, CLU inhibited the expression of mechanical stress-stimulated and TGF-β1-stimulated COL1A2 and α-SMA. Mechanistic studies showed that CLU inhibited mechanical stress-stimulated and TGF-β1-induced SMAD3 activ

SUBMITTER: Liu C 

PROVIDER: S-EPMC9534863 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature