2026-07-21T14:15:06Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/156762024-09-27T09:15:53Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Lehmann, Guillermo L author Ginsberg, Michael author Nolan, Daniel J author Rodríguez, Cristina author Martínez-González, José author Zeng, Shemin author Voigt, Andrew P author Mullins, Robert F author Rafii, Shahin author Rodriguez-Boulan, Enrique author Benedicto, Ignacio author 2022-09-24 Alpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium (RPE)-conditioned medium induces A2M expression specifically in ECs. Experiments using chemical inhibitors, blocking antibodies, and recombinant proteins revealed a key role of VEGF-A in RPE-mediated A2M induction in ECs. Furthermore, incubation of ECs with RPE-conditioned medium reduces matrix metalloproteinase-2 gelatinase activity of culture supernatants, which is partially restored after A2M knockdown in ECs. We propose that dysfunctional RPE or choroidal blood vessels, as observed in retinal diseases such as age-related macular degeneration, may disrupt the crosstalk mechanism we describe here leading to alterations in the homeostasis of choroidal ECM, Bruch's membrane and visual function. Cells. 2022 Sep 24;11(19):2975 10.3390/cells11192975 2073-4409 Cells 36230937 http://hdl.handle.net/20.500.12105/15676 Retinal Pigment Epithelium-Secreted VEGF-A Induces Alpha-2-Macroglobulin Expression in Endothelial Cells.