Pulmonary Arterial Hypertension KnowledgeBase (PAHKB)
PAHKB
Pulmonary Arterial Hypertension KnowledgeBase
General information | Literature | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID

2353

Name

FOS

Synonymous

AP-1|C-FOS|p55;FBJ murine osteosarcoma viral oncogene homolog;FOS;FBJ murine osteosarcoma viral oncogene homolog

Definition

FBJ murine osteosarcoma viral (v-fos) oncogene homolog (oncogene FOS)|G0/G1 switch regulatory protein 7|activator protein 1|cellular oncogene c-fos|proto-oncogene c-Fos

Position

14q24.3

Gene type

protein-coding

Source

Count: FOS; 2353

Sentence

Abstract

"Serotonin transporter, sex, and hypoxia: microarray analysis in the pulmonary arteries of mice identifies genes with relevance to human PAH."

pulmonary arterial hypertension (PAH) is up to threefold more prevalent in women than men. Female mice overexpressing the serotonin transporter (SERT; SERT+ mice) exhibit PAH and exaggerated hypoxia-induced PAH, whereas male SERT+ mice remain unaffected. To further investigate these sex differences, microarray analysis was performed in the pulmonary arteries of normoxic and chronically hypoxic female and male SERT+ mice. Quantitative RT-PCR analysis was employed for validation of the microarray data. In relevant groups, immunoblotting was performed for genes of interest (CEBPbeta, CYP1B1, and FOS). To translate clinical relevance to our findings, CEBPbeta, CYP1B1, and FOS mRNA and protein expression was assessed in pulmonary artery smooth muscle cells (PASMCs) derived from idiopathic PAH (IPAH) patients and controls. In female SERT+ mice, multiple pathways with relevance to PAH were altered. This was also observed in chronically hypoxic female SERT+ mice. We selected 10 genes of interest for qRT-PCR analysis (FOS, CEBPbeta, CYP1B1, MYL3, HAMP2, LTF, PLN, NPPA, UCP1, and C1S), and 100% concordance was reported. Protein expression of three selected genes, CEBPbeta, CYP1B1, FOS, was also upregulated in female SERT+ mice. Serotonin and 17beta-estradiol increased CEBPbeta, CYP1B1, and FOS protein expression in PASMCs. In addition, CEBPbeta, CYP1B1, and FOS mRNA and protein expression was also increased in PASMCs derived from IPAH patients. Here, we have identified a number of genes that may predispose female SERT+ mice to PAH, and these findings may also be relevant to human PAH.

"Serotonin transporter, sex, and hypoxia: microarray analysis in the pulmonary arteries of mice identifies genes with relevance to human PAH."

pulmonary arterial hypertension (PAH) is up to threefold more prevalent in women than men. Female mice overexpressing the serotonin transporter (SERT; SERT+ mice) exhibit PAH and exaggerated hypoxia-induced PAH, whereas male SERT+ mice remain unaffected. To further investigate these sex differences, microarray analysis was performed in the pulmonary arteries of normoxic and chronically hypoxic female and male SERT+ mice. Quantitative RT-PCR analysis was employed for validation of the microarray data. In relevant groups, immunoblotting was performed for genes of interest (CEBPbeta, CYP1B1, and FOS). To translate clinical relevance to our findings, CEBPbeta, CYP1B1, and FOS mRNA and protein expression was assessed in pulmonary artery smooth muscle cells (PASMCs) derived from idiopathic PAH (IPAH) patients and controls. In female SERT+ mice, multiple pathways with relevance to PAH were altered. This was also observed in chronically hypoxic female SERT+ mice. We selected 10 genes of interest for qRT-PCR analysis (FOS, CEBPbeta, CYP1B1, MYL3, HAMP2, LTF, PLN, NPPA, UCP1, and C1S), and 100% concordance was reported. Protein expression of three selected genes, CEBPbeta, CYP1B1, FOS, was also upregulated in female SERT+ mice. Serotonin and 17beta-estradiol increased CEBPbeta, CYP1B1, and FOS protein expression in PASMCs. In addition, CEBPbeta, CYP1B1, and FOS mRNA and protein expression was also increased in PASMCs derived from IPAH patients. Here, we have identified a number of genes that may predispose female SERT+ mice to PAH, and these findings may also be relevant to human PAH.

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