Maternal smoking during pregnancy aggravated muscle phenotype in FHL1−/y offspring mice similar to congenital clubfoot through P2RX7-mediated pyroptosis. (1st July 2021)

• Record Type: Journal Article
• Authors: Lou, Yi; Miao, Jianing; Li, Fang; Ding, Jingjing; Wang, Lili
• Is Part Of: Toxicology letters. Volume 345(2021)
• Page Start: 54
• Page End: 60
• Publication Date: 2021-07-01
• Subjects: FHL1 -- Congenital clubfoot -- Cigarette smoke -- Skeletal muscle -- P2RX7 -- Pyroptosis; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.04.014
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Maternal smoking aggravated muscle phenotype in FHL1 −/y offspring mice. P2RX7-mediated pyroptosis participated in aggravated muscle phenotype. Cytoskeletal proteins-MYBPC2, LDB3 involved in aggravated muscle phenotype. Abstract: Congenital clubfoot (CCF) is a common birth defect. Maternal smoking during pregnancy increases the risk of CCF. In previous research, we found muscle phenotypes similar to CCF in four and a half LIM domain protein 1 ( FHLI ) offspring mice ( FHL1 −/y ). However, the role of P2RX7-mediated pyroptosis in the effect of cigarette smoke (CS) on the skeletal muscle of FHL1 −/y mice during pregnancy is unclear. In the present study, pregnant mice at 11 days of gestation were exposed to CS and male offspring of wild-type (WT) and FHL1 −/y mice were divided into four groups (Control-WT, Control-KO, CS-WT, CS-KO). The histomorphology of lower limb muscles was examined using hematoxylin and eosin (H&E) staining. P2RX7, indicators of pyroptosis (NLRP3, ASC, cleaved-caspase 1, IL-1β), and cytoskeletal proteins (MYBPC2, LDB3) were also detected using immunoblotting. CS exposure during pregnancy aggravated the muscle phenotype similar to CCF in FHL1 −/y offspring mice. FHL1 gene knockout (KO) or CS exposure during pregnancy each activated the expression of P2RX7, cell pyroptosis-related proteins (NLRP3, ASC, cleaved-caspase 1, IL-1β), a muscle injury marker (MYOD1), and cytoskeletal proteins (MYBPC2, LDB3); these two factors had an additive effect. The results showed maternal smoking during pregnancy aggravated muscle phenotype similar to CCF in FHL 1 −/y offspring mice through P2RX7-mediated pyroptosis.