Role of complement 3a in the growth of mesangial cells from stroke-prone spontaneously hypertensive rats
Role of complement 3a in the growth of mesangial cells from stroke-prone spontaneously hypertensive rats
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DOI：
10.3109/10641963.2013.789042
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发表时间：
2014-01-01
影响因子：
12.3
通讯作者：
Matsumoto, Koichi
中科院分区：
文献类型：
--
作者：
Ikeda, Kazuya;Fukuda, Noboru;Matsumoto, Koichi
来源于自发性高血压大鼠（SHR）的血管平滑肌细胞（VSMC）表现出过度生长，具有合成表型和血管紧张素II（Ang II）产生，并与补体（C3）产生增加相关。我们假设C3参与高血压大鼠系膜细胞（MCs）的生长。我们研究了一种C3 a受体抑制剂对易卒中的自发性高血压大鼠（SHR）-SP、SHR和Wistar-Kyoto（WKY）大鼠MC增殖、表型和Ang II生成的影响。肾皮质C3和C3 a受体的表达通过免疫组织化学染色来评估。我们研究了C3 a抑制剂SB 290157对SHR-SP、SHR和WKY大鼠细胞增殖、表型标记物mRNA表达和Ang II产生的影响。SHR和SHRSP肾小球中C3免疫染色较强。SHR-SP和SHR的MCs大量表达前原C3 mRNA。SB 290157显著抑制SHR-SP和SHR系膜细胞的DNA合成和增殖。SB 290157处理可降低SHRSP和SHR MC中骨桥蛋白mRNA的表达，同时降低MC中α-SMA mRNA的基础表达。SB 290157可显著降低SHR和SHR-SP系膜细胞Ang Ⅱ的生成。内源性C3 a促进了合成表型的过度生长以及SHR-SP和SHR MCs中Ang II的产生。C3和C3 a受体系统可能主要参与了高血压大鼠肾脏重构的发病机制。
Vascular smooth muscle cells (VSMCs) derived from spontaneously hypertensive rats (SHR) show exaggerated growth with a synthetic phenotype and angiotensin II (Ang II) production associated with increased production of complement (C3). We hypothesized that C3 is involved in the growth of mesangial cells (MCs) from hypertensive rats. We examined the effects of a C3a receptor inhibitor on proliferation, phenotype and Ang II generation in MCs from stroke prone-spontaneously hypertensive rats (SHR)-SP, SHR and Wistar-Kyoto (WKY) rats. Expression of C3 and C3a receptor were evaluated by immunohistochemical staining of the renal cortex. We examined the effects of the C3a inhibitor, SB290157, on proliferation, the expression of phenotype-marker mRNAs and Ang II production in cells from SHR-SP, SHR and WKY rats. Immunostaining of C3 was stronger in SHR and SHRSP glomeruli. MCs from SHR-SP and SHR abundantly express pre-pro C3 mRNA. SB290157 significantly inhibited basal DNA synthesis and proliferation of MCs from SHR-SP and SHR. Expression of osteopontin mRNA in MCs from SHRSP and SHR was decreased with SB290157 treatment, whereas MC basal expression of alpha-SMA mRNA was decreased. SB290157 significantly decreased the production of Ang II in MCs from SHR-SP and SHR. Endogenous C3a promotes exaggerated growth with a synthetic phenotype and the production of Ang II in MCs from SHR-SP and SHR. The C3 and C3a receptor system may primarily be involved in the pathogenesis of renal remodeling in hypertensive rats.