Mesangial Cells and Glomerular Endothelial Cells Crosstalk in Rat Anti-Thy-1 Nephritis through VEGFA/VEGFAR2 and Angpt2/Tie2 pathway

BACKGROUNDMesangial proliferative glomerulonephritis is characterized by the proliferation of mesangial cells (MCs). Endothelial cells (ECs) are affected by signals from MCs, resulting in capillary proliferation, but the specific signaling pathway associated with this activity remains unclear.RESULTSIn this study, the expression of PCNA, RECA-1 and CD34 in the glomeruli increased on the 7th day after anti-Thy-1 nephritis establishment, indicating the occurrence of ECs proliferation. After coculturing MCs and ECs in vitro, we observed that activated MCs could promote ECs proliferation, migration and α-SMA expression. Moreover, activated ECs had the same effects on MCs. RT-qPCR showed that activated MCs could increasingly secrete VEGFA, and Angpt2 expression in VEGFA-activated ECs was enhanced. Considering that Angpt2-mediated inhibition of ECs surface receptor Tie2 phosphorylation causes ECs proliferation, we hypothesized that VEGFA/VEGFR2 and Angpt2/Tie2 signaling is involved in the interaction between MCs and ECs. Our results showed that blocking VEGFA or adding the Angpt2 antagonist Angpt1 to the coculture system decreased the number of EdU-positive cells，Angpt2，p-VEGFR2 and p-MAPK expression, but increased p-Tie2 in ECs. To determine whether Angpt1 could effectively alleviate the pathological changes of anti-Thy-1 nephritis, we performed Vasculotide (Angpt1 mimic peptide) treatment assays in vivo. The results confirmed that the addition of Vasculotide could effectively reduce PCNA, RECA-1 and α-SMA expression and promote p-Tie2.CONCLUSIONIn summary, the study showed that the VEGFA/VEGFR2 and Angpt2/Tie2 signaling pathway mediate interactions between MCs and ECs, providing an important theoretical basis for the treatment of mesangial proliferative glomerulonephritis.