Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/15676
Retinal Pigment Epithelium-Secreted VEGF-A Induces Alpha-2-Macroglobulin Expression in Endothelial Cells.
Cells. 2022 Sep 24;11(19):2975
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.
Pregnancy-Associated alpha 2-Macroglobulins | Retinal Pigment Epithelium | Antibodies, Blocking | Culture Media, Conditioned | Endothelial Cells | Female | Gelatinases | Humans | Matrix Metalloproteinase 2 | Pregnancy | Protease Inhibitors | Recombinant Proteins | Transcription Factors | Vascular Endothelial Growth Factor A
Files in this item
- Retinal Pigment Epithelium Cells ...