RGD Reference Report - SOX17 is a Critical Factor in Maintaining Endothelial Function in Pulmonary Hypertension by an Exosome-Mediated Autocrine Manner. - Rat Genome Database

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SOX17 is a Critical Factor in Maintaining Endothelial Function in Pulmonary Hypertension by an Exosome-Mediated Autocrine Manner.

Authors: Zou, Xiaozhou  Liu, Ting  Huang, Zhongjie  Zhou, Wei  Yuan, Mengnan  Zhao, Hongying  Pan, Zongfu  Chen, Pengcheng  Shao, Yanfei  Hu, Xiaoping  Zhang, Su  Zheng, Shuilian  Zhang, Yiwen  Huang, Ping 
Citation: Zou X, etal., Adv Sci (Weinh). 2023 May;10(14):e2206139. doi: 10.1002/advs.202206139. Epub 2023 Mar 15.
RGD ID: 329853737
Pubmed: PMID:36919784   (View Abstract at PubMed)
PMCID: PMC10190640   (View Article at PubMed Central)
DOI: DOI:10.1002/advs.202206139   (Journal Full-text)

Endothelial dysfunction is considered a predominant driver for pulmonary vascular remodeling in pulmonary hypertension (PH). SOX17, a key regulator of vascular homoeostasis, has been found to harbor mutations in PH patients, which are associated with PH susceptibility. Here, this study explores whether SOX17 mediates the autocrine activity of pulmonary artery ECs to maintain endothelial function and vascular homeostasis in PH and its underlying mechanism. It is found that SOX17 expression is downregulated in the endothelium of remodeled pulmonary arteries in IPH patients and SU5416/hypoxia (Su/hypo)-induced PH mice as well as dysfunctional HPAECs. Endothelial knockdown of SOX17 accelerates the progression of Su/hypo-induced PH in mice. SOX17 overexpression in the pulmonary endothelium of mice attenuates Su/hypo-induced PH. SOX17-associated exosomes block the proliferation, apoptosis, and inflammation of HPAECs, preventing pulmonary arterial remodeling and Su/hypo-induced PH. Mechanistic analyses demonstrates that overexpressing SOX17 promotes the exosome-mediated release of miR-224-5p and miR-361-3p, which are internalized by injured HPAECs in an autocrine manner, ultimately repressing the upregulation of NR4A3 and PCSK9 genes and improving endothelial function. These results suggest that SOX17 is a key gene in maintaining endothelial function and vascular homeostasis in PH through regulating exosomal miRNAs in an autocrine manner.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SOX17Humanprimary pulmonary hypertension  IEP protein:decreased expression:pulmonary artery (human)RGD 
Sox17Ratprimary pulmonary hypertension  ISOSOX17 (Homo sapiens)protein:decreased expression:pulmonary artery (human)RGD 
Sox17Mouseprimary pulmonary hypertension  ISOSOX17 (Homo sapiens)protein:decreased expression:pulmonary artery (human)RGD 
SOX17HumanPulmonary Hypertension, Hypoxia-Induced  ISOSox17 (Mus musculus)protein:decreased expression:pulmonary artery endothelium (mouse)RGD 
Sox17RatPulmonary Hypertension, Hypoxia-Induced  ISOSox17 (Mus musculus)protein:decreased expression:pulmonary artery endothelium (mouse)RGD 
Sox17MousePulmonary Hypertension, Hypoxia-Induced  IEP protein:decreased expression:pulmonary artery endothelium (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sox17  (SRY-box transcription factor 17)

Genes (Mus musculus)
Sox17  (SRY (sex determining region Y)-box 17)

Genes (Homo sapiens)
SOX17  (SRY-box transcription factor 17)


Additional Information