Galectin-1 Modulates Cell Adhesions, Caveolae, and Vascular Permeability in Kidney Endothelial Cells - Insights from Proteomics

ABSTRACT: Microvascular inflammation and endothelial injury, triggered by interferon-gamma (IFNgamma), are hallmarks of antibody-mediated rejection (ABMR), the leading cause of premature kidney allograft loss. Chronic ABMR exhibits glomerular basement membrane and extracellular matrix (ECM) remodeling and endothelial caveolae formation. Galectin-1, an immunomodulatory protein that interacts with the ECM, was found to be increased in the glomeruli of patients with ABMR and dysregulated on the gene and protein level by IFNgamma. Mechanisms underlying endothelial dysfunction in ABMR and its links to ECM remodeling remain incompletely understood, particularly in the context of proteins such as galectin-1. Here we studied the effects of galectin-1 modulation in glomerular microvascular endothelial cells (GMECs) in vitro. We demonstrated that galectin-1 was mainly expressed by GMECs in ABMR kidneys. To model key aspects of endothelial injury in ABMR we knocked down LGALS1 in GMECs, followed by stimulation with IFNgamma and performed label-free quantitative proteomic profiling of GMECs. Proteomic analysis identified 5446 proteins (FDR<0.01), of which 236, 827, and 267 were significantly dysregulated in response to LGALS1 knockdown, IFNgamma treatment, and their interaction, respectively (FDR<0.05). Both LGALS1 knockdown and the interaction between treatments increased expression of adhesion proteins (FDR<0.01), particularly integrin subunit B5, which was validated. Thus, endothelial signaling pathways regulated by inflammatory cues and galectin-1 may contribute to endothelial injury, highlighting this glycan-binding protein, galectin-1, as a potential therapeutic target in ABMR.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Kidney

SUBMITTER: Alex Boshart  

LAB HEAD: Ana Konvalinka

PROVIDER: PXD074919 | Pride | 2026-10-15

REPOSITORIES: Pride