LIM and SH3 protein 2 (Lasp2) is a novel pregnane X receptor target gene in mouse liver

• DOI: 10.1016/j.molpha.2025.100019
• Publication Date: 2025-02-07T23:54:31Z
• Authors: Anja Konzack; Mikko Karpale; Tomas Smutny; Mohamed Hassanen; Piia Lassila; Maria H. Ahonen; Mahmoud-Sobhy Elk...; Outi Kummu; Petr Pavek; Jukka Hakkola
• Keywords: Pregnane X receptor

LIM and Src homology 3 (SH3) protein 2 (LASP2) is a small focal adhesion first identified as splice variant of the nebulette gene (Nebl). As newest member nebulin family, regulation function LASP2 remain largely unknown. Our previous RNA-sequencing results Nebl one most highly induced genes in mouse liver response to activation pregnane X receptor (PXR). In this study, we investigated phenomenon further show that PXR induces Lasp2 instead Nebl, which partially use same exons. was found be ligand pregnenolone 16α-carbonitrile (PCN) treatment vivo both after 4-day long-term, 28-day male female mice. Interestingly, induction more efficient high-fat diet-fed mice (103-fold PCN treatment) than normal chow-fed (32-fold treatment). abolished knockout but could rescued by re-expression PXR, indicating mediated. primary hepatocytes cycloheximide did not inhibit binding site recognized upstream suggesting direct PXR. human 3D hepatocytes, rifampicin only modest increase expression. This study shows for time strongly expression establishes novel target gene. SIGNIFICANCE STATEMENT: have previously (Nebl) efficiently activating compounds. (Lasp2) coding partly sharing exons with liver.