2012;109(25):10024\10029. vitro triggered MCs\expressed VEGFA to promote vascular endothelial growth factor receptor2 (VEGFR2) activation, Angpt2 expression and ECs proliferation, but inhibit TEK tyrosine kinase (Tie2) phosphorylation. MCs\derived VEGFA Rabbit Polyclonal to PARP (Cleaved-Asp214) stimulated Angpt2 expression in ECs, which inhibited Tie2 phosphorylation and promoted ECs proliferation. And decline of Tie2 phosphorylation induced ECs proliferation. In anti\Thy\1 nephritis, promoting Tie2 phosphorylation could alleviate ECs proliferation. Conclusions Our study showed that activated MCs promoted ECs proliferation through VEGFA/VEGFR2 and Angpt2/Tie2 pathway in experimental mesangial proliferative glomerulonephritis (MPGN) and in vitro co\culture system. And enhancing Connect2 phosphorylation could alleviate ECs proliferation, which will provide a new idea for MPGN treatment. Keywords: Angpt2/Tie2 pathway, glomerular endothelial cells, mesangial cells, mesangial proliferative glomerulonephritis, VEGFA/VEGFR2 pathway The underlying mechanism of glomerular ECs proliferation. Normally, Angpt2 was stored in the Weibel\Palade body in ECs. When MCs were stimulated, they produced VEGFA which acted around the ECs surface receptor VEGFR2 to promote Angpt2 expression. Angpt2 acted on Tie2 through autocrine which inhibited Tie2 phosphorylation and caused ECs proliferation. ECs, endothelial cells. MCs, mesangial cells. VEGFA, vascular endothelial growth factor Patchouli alcohol A. VEGFR2, vascular endothelial growth factor receptor2. Angpt2, angiopoietin2. Tie2, TEK tyrosine kinase. 1.?INTRODUCTION Mesangial proliferative glomerulonephritis (MPGN) is characterized by mesangial cells (MCs) proliferation and increased extracellular matrix deposition. 1 , 2 , 3 , 4 As the most common pathological switch of main glomerulonephritis worldwide, MPGN prospects to glomerular fibrosis and sclerosis and eventually results in end\stage renal disease. Patchouli alcohol 5 Anti\Thy\1 nephritis is the most suitable animal model to study the specific pathogenesis of MPGN. 5 , Patchouli alcohol 6 It shows that as MCs were damaged, glomerular capillaries proliferated and developed aneurysmal changes, 7 and as MCs continued to return to normal, the aneurysm gradually decreased. 8 , 9 Therefore, there might be cell\cell communication between MCs and ECs, which leads that mesangial areas and the capillaries switch synchronously. And strategies to prevent such cell\cell communication would be useful in the resolution of vascular lesions in MPGN. Vascular endothelial growth factor (VEGF) plays significant role in angiogenesis, tumour growth, development and atherosclerosis, which mainly produced by podocytes, distal tubules and collecting duct epithelial cells in normal human and rat kidneys. 10 As a dimer protein, it composed of 121, 165, 189 or 206 amino acids, respectively. VEGF165, VEGFA, is the most common isoform and it has been verified that VEGFA expressed in activated MCs of experimental MPGN. 11 TEK tyrosine kinase (Tie2) is expressed on the surface of Patchouli alcohol ECs and is a tyrosine kinase receptor with two homologous domains, IG and EGF. 12 Angiopoietin1 (Angpt1) and angiopoietin2 (Angpt2) competitively bind to Tie2, which is usually important in angiogenesis and vascular inflammation. Angpt1 binds to Tie2 to promote Connect2 phosphorylation, thereby maintaining vascular structural integrity, protecting ECs from apoptosis and inhibiting the inflammatory response. 13 , 14 , 15 Angpt2 is usually expressed and stored in the Weibel\Palade body of ECs, interfering with the Angpt1/Tie2 signalling pathway. 16 , 17 VEGFA and Angpt2 both are considered as pro\angiogenesis factors. 18 , 19 , 20 Martina Schmittnaegel et al pointed out that Angpt2 and VEGFA bispecial\antibody (A2V).
T-Type Calcium Channels