| Autor: |
Colvert, C. Alex, Hawkins, Kennedy P., Semenikhina, Marharyta, Stefanenko, Mariia, Pavlykivska, Olesia, Oates, Jim C., DeLeon-Pennell, Kristine Y., Palygin, Oleg, Van Beusecum, Justin P. |
| Zdroj: |
American Journal of Physiology - Renal Physiology; 20240101, Issue: Preprints |
| Abstrakt: |
Increased mechanical endothelial cell stretch contributes to the development of numerous cardiovascular and renal pathologies. Recent studies have shined a light on the importance of sex-dependent inflammation in the pathogenesis of renal disease states. The endothelium plays an intimate and critical role in the orchestration of immune cell activation through upregulation of adhesion molecules and secretion of cytokines and chemokines. While endothelial cells are not recognized as professional antigen presenting cells, in response to cytokine stimulation, endothelial cells can express both major histocompatibility complexes (MHC) I and II. MHCs are essential to form part of the immunological synapse interface during antigen presentation to adaptive immune cells. Whether MHC I and II are increased under increased mechanical stretch is unknown. Due to hypertension being multifactorial, we hypothesized that increased mechanical endothelial stretch promotes the regulation of MHCs and key costimulatory proteins on mouse renal endothelial cells (MRECs) in a stretch-dependent manner. MRECs derived from both sexes underwent 5%, 10%, or 15% uniaxial cyclical stretch, and immunological synapse interface proteins were determined by immunofluorescence microscopy, immunoblotting, and RNA sequencing. We found that increased endothelial mechanical stretch conditions promoted downregulation of MHC I in male but upregulation in female MRECs. Moreover, MHC II was upregulated by mechanical stretch in both male and female MRECs, with CD86 and CD70 were regulated in a sex-dependent manner. By bulk RNA sequencing, we found that increased mechanical endothelial cell stretch promotes differential gene expression of key antigen processing and presentation genes in female MRECs, demonstrating that females have upregulation of key antigen presentation pathways. Taken together, our data demonstrate that mechanical endothelial stretch regulates endothelial activation and immunological synapse interface formation in renal endothelial cells in a sex-dependent manner. |
| Databáze: |
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