Effect of bradykinin on renal mesangial cell proliferation and extracellular matrix secretion

Abstract

ABSTRACT. Recent studies have found that bradykinin (BK) plays a role in delaying glomerulosclerosis, although the mechanism of this phenomenon remains unclear. Mesangial cell proliferation (MCP) and extracellular matrix (ECM) secretion are important mechanisms for glomerulosclerosis. This study investigated the impact of BK on the platelet-derived growth factor (PDGF)-induced proliferation of mesangial cells, and evaluated its correlations with the extracellular signal-related kinase (ERK) signaling pathway. The results showed that on its own, 10-1000 mg/L BK promoted MCP and ECM secretion and induced ERK phosphorylation. However, BK administration after PDGF pre-incubation inhibited PDGF-induced MCP, ECM secretion, and ERK phosphorylation. The BK B2 receptor-specific antagonist, HOE-140, and tyrosine phosphatase inhibitor (OV) effectively blocked the function of BK. In summary, these results demonstrated that BK has a bidirectional effect on MCP and ECM secretion: when used alone, it promoted effects on these phenomena, but these effects were inhibited when combined with PDGF. This suggests that the role of BK might be achieved through inhibiting activation of the PDGF-induced ERK1/2 pathway.

Effect of immunosuppression on the human mesangial cell cycle

“…The proliferation of mesangial cells is a common pathological feature of glomerular diseases, including IgA nephropathy and lupus nephritis ( 11 ). For these reasons, numerous studies have investigated the contribution of mesangial cells to the development of glomerulosclerosis ( 15 ). However, these studies have concentrated on cultured cells or animal models of glomerular injury and there have been few studies of human mesangial cells.…”

Effect of bradykinin on TGF-β1-induced retinal pigment epithelial cell proliferation and extracellular matrix secretion

“…Nelly Blaes reported that BK inhibits TGF-β-induced collagen production by activating the bradykinin B2 receptor (B2R) [27]. Other studies have found that BK inhibits growth factor-induced cell proliferation and ECM secretion [28]. However, the effects of BK on cultured RPE cell proliferation and the mechanism underlying its effects on TGF-β1 remain unknown.…”