Temporal expression of autocrine growth factors corresponds to morphological features of mesangial proliferation in Habu snake venom-induced glomerulonephritis.
Temporal expression of autocrine growth factors corresponds to morphological features of mesangial proliferation in Habu snake venom-induced glomerulonephritis.
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发表时间：
1993-11
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通讯作者：
J. Barnes;H. Abboud
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作者：
J. Barnes;H. Abboud
哈布蛇毒会诱发加速系膜增生性肾小球肾炎，并在 72 小时内遵循从早期毛细血管动脉瘤到由汇合系膜细胞组成的微结节的可预测过程。我们从形态学角度检查了系膜细胞增殖过程，并将其与编码两种肽生长因子、血小板源性生长因子 (PDGF) A 和 B 链以及转化生长因子-β (TGF-β) 的信使 (m) RNA 的表达相关联。对大鼠进行肾切除术，24小时后注射哈布蛇毒液或盐水。 24、48和72小时后获得肾皮质和分离的肾小球，用于组织学评估、mRNA的制备和Northern分析，以及使用识别A链和B链的多克隆抗体对PDGF进行免疫组织化学定位。 PDGF B链mRNA的最大表达发生在24小时和系膜细胞增殖开始之前；而PDGF A链和TGF-β mRNA的最大表达发生在48小时和活跃的系膜细胞增殖期间。与单肾切除术和盐水对照相比，当PDGF A链下降且PDGF B链不表达时，以及当病变内的系膜细胞达到汇合且增殖消退时，TGF-β mRNA的表达持续72小时。 PDGF蛋白在24和48小时定位于与血小板相关的肾小球病变中，并在48和72小时定位于系膜细胞内。这些结果与PDGF和TGF-β分别作为体外系膜细胞生长的正调节剂和负调节剂的已知作用一致，并表明这些因子的表达的相对平衡可能在体内肾小球疾病中发挥作用。
Habu snake venom induces an accelerated mesangial proliferative glomerulonephritis that follows a predictable course from early capillary aneurysms to micronodules comprised of confluent mesangial cells within 72 hours. We examined morphologically the course of mesangial cell proliferation and correlated it with the expression of messenger (m) RNA encoding two peptide growth factors, platelet-derived growth factor (PDGF) A and B chains and transforming growth factor-beta (TGF-beta). Rats were uninephrectomized and 24 hours later injected with Habu snake venom or saline. Kidney cortex and isolated glomeruli were obtained 24, 48, and 72 hours later for histological assessment, preparation and Northern analysis of mRNA, and immunohistochemical localization of PDGF using a polyclonal antibody that recognizes A and B chains. Maximal expression of PDGF B chain mRNA occurred at 24 hours and before the onset of mesangial cell proliferation; whereas maximal expression of PDGF A chain and TGF-beta mRNA occurred at 48 hours and during active mesangial cell proliferation. Expression of TGF-beta mRNA persisted at 72 hours at a time when PDGF A chain declined and PDGF B chain was not expressed compared to uninephrectomy and saline controls and at a time when mesangial cells within lesions reached confluence and proliferation subsided. PDGF protein localized in glomerular lesions associated with platelets at 24 and 48 hours and within mesangial cells at 48 and 72 hours. These results agree with the known roles of PDGF and TGF-beta as positive and negative modulators, respectively, of mesangial cell growth in vitro and suggest that a relative balance of the expression of these factors may operate in glomerular disease in vivo.