Stimulatory G-Protein α Subunit Modulates Endothelial Cell Permeability Through Regulation of Plasmalemma Vesicle-Associated Protein

被引：7

作者：

He, Lifan ^{[1
,7
]}

Lu, Hanlin ^{[1
,7
]}

Ji, Xuyang ^{[1
,2
,7
]}

Chu, Jianying ^{[3
]}

Qin, Xiaoteng ^{[1
,7
]}

Chen, Min ^{[4
]}

Weinstein, Lee S. ^{[4
]}

Gao, Jiangang ^{[5
,6
]}

Yang, Jianmin ^{[1
,7
]}

Zhang, Qunye ^{[1
,7
]}

Zhang, Cheng ^{[1
,7
]}

Zhang, Wencheng ^{[1
,2
,7
]}

机构：

[1] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Chinese Natl Hlth Commiss, Jinan, Peoples R China

[2] Shandong First Med Univ, Cent Hosp, Cardiovasc Dis Res Ctr, Jinan, Peoples R China

[3] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan, Peoples R China

[4] Natl Inst Diabet Digest & Kidney Dis, NIH, Metab Dis Branch, Bethesda, MD USA

[5] Shandong Univ, Sch Life Sci, Jinan, Peoples R China

[6] Shandong Univ, Key Lab Minist Educ Expt Teratol, Jinan, Peoples R China

[7] Shandong Univ, Qilu Hosp, Chinese Acad Med Sci, Cheeloo Coll Med,State & Shandong Prov Joint Key L, Jinan, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

endothelial permeability; Gsa; CREB; PLVAP; edema; ACTIVATION; PV1; PHOSPHORYLATION; DIAPHRAGMS; COMPONENT; BINDING; GROWTH; PV-1;

D O I：

10.3389/fphar.2022.941064

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Endothelial cell leakage occurs in several diseases. Intracellular junctions and transcellular fashion are involved. The definite regulatory mechanism is complicated and not fully elucidated. The alpha subunit of the heterotrimeric G-stimulatory protein (Gs alpha) mediates receptor-stimulated production of cyclic adenosine monophosphate (cAMP). However, the role of Gs alpha in the endothelial barrier remains unclear. In this study, mice with knockout of endothelial-specific Gs alpha (Gs alpha(ECKO)) were generated by crossbreeding Gs alpha(flox/flox) mice with Cdh5-CreER(T2) transgenic mice, induced in adult mice by tamoxifen treatment. Gs alpha(ECKO) mice displayed phenotypes of edema, anemia, hypoproteinemia and hyperlipoproteinemia, which indicates impaired microvascular permeability. Mechanistically, Gs alpha deficiency reduces the level of endothelial plasmalemma vesicle-associated protein (PLVAP). In addition, overexpression of Gs alpha increased phosphorylation of cAMP response element-binding protein (CREB) as well as the mRNA and protein levels of PLVAP. CREB could bind to the CRE site of PLVAP promoter and regulate its expression. Thus, Gs alpha might regulate endothelial permeability via cAMP/CREB-mediated PLVAP expression.

引用

页数：13

共 41 条

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