| First Author | He L | Year | 2022 |
| Journal | Front Pharmacol | Volume | 13 |
| Pages | 941064 | PubMed ID | 35721211 |
| Mgi Jnum | J:326439 | Mgi Id | MGI:7293662 |
| Doi | 10.3389/fphar.2022.941064 | Citation | He L, et al. (2022) Stimulatory G-Protein alpha Subunit Modulates Endothelial Cell Permeability Through Regulation of Plasmalemma Vesicle-Associated Protein. Front Pharmacol 13:941064 |
| abstractText | 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 (Gsalpha) mediates receptor-stimulated production of cyclic adenosine monophosphate (cAMP). However, the role of Gsalpha in the endothelial barrier remains unclear. In this study, mice with knockout of endothelial-specific Gsalpha (Gsalpha(ECKO)) were generated by crossbreeding Gsalpha(flox/flox) mice with Cdh5-CreER(T2) transgenic mice, induced in adult mice by tamoxifen treatment. Gsalpha(ECKO) mice displayed phenotypes of edema, anemia, hypoproteinemia and hyperlipoproteinemia, which indicates impaired microvascular permeability. Mechanistically, Gsalpha deficiency reduces the level of endothelial plasmalemma vesicle-associated protein (PLVAP). In addition, overexpression of Gsalpha 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, Gsalpha might regulate endothelial permeability via cAMP/CREB-mediated PLVAP expression. |
