2026-08-30T13:04:44Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/158792025-05-16T06:40:30Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Meghadri, Sri Harsha author Martinez-Delgado, Beatriz author Ostermann, Lena author Gomez-Mariano, Gema Maria author Perez-Luz, Sara author Tumpara, Srinu author Wrenger, Sabine author DeLuca, David S author Maus, Ulrich A author Welte, Tobias author Janciauskiene, Sabina author 2022-09-09 The SERPINA1 gene encodes alpha1-antitrypsin (AAT), an acute phase glycoprotein and serine protease inhibitor that is mainly (80-90%) produced in the liver. Point mutations in the SERPINA1 gene can lead to the misfolding, intracellular accumulation, and deficiency of circulating AAT protein, increasing the risk of developing chronic liver diseases or chronic obstructive pulmonary disease. Currently, siRNA technology can knock down the SERPINA1 gene and limit defective AAT production. How this latter affects other liver genes is unknown. Livers were taken from age- and sex-matched C57BL/6 wild-type (WT) and Serpina1 knockout mice (KO) aged from 8 to 14 weeks, all lacking the five serpin A1a-e paralogues. Total RNA was isolated and RNA sequencing, and transcriptome analysis was performed. The knockout of the Serpina1 gene in mice changed inflammatory, lipid metabolism, and cholesterol metabolism-related gene expression in the liver. Independent single-cell sequencing data of WT mice verified the involvement of Serpina1 in cholesterol metabolism. Our results from mice livers suggested that designing therapeutic strategies for the knockout of the SERPINA1 gene in humans must account for potential perturbations of key metabolic pathways and consequent mitigation of side effects. Int J Mol Sci. 2022 Sep 9;23(18):10425. 10.3390/ijms231810425 1422-0067 International journal of molecular sciences 36142337 http://hdl.handle.net/20.500.12105/15879 Liver SERPINA Mice Gene knockout RNA sequencing Transcriptomics Metabolism Single-cell Alpha1-antitrypsin Protein misfolding Data analysis Loss of Serpina1 in Mice Leads to Altered Gene Expression in Inflammatory and Metabolic Pathways