2026-08-30T13:04:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/158792025-05-16T06:40:30Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
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
funder
Instituto de Salud Carlos III
2023-04-24T13:58:37Z
2023-04-24T13:58:37Z
2022-09-09
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
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.
eng
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
research article
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