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首页> 外文期刊>American Journal of Physiology >Extracellular matrix regulates glomerular epithelial cell survival and proliferation.
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Extracellular matrix regulates glomerular epithelial cell survival and proliferation.

机译：细胞外基质调节肾小球上皮细胞的存活和增殖。

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Glomerular epithelial cell (GEC) injury and apoptosis may contribute to sclerosis in glomerulonephritis. The present study addresses signals that regulate survival of GEC in culture and in the acute puromycin aminonucleoside nephrosis (PAN) model of GEC injury in vivo. Compared with GEC on plastic substratum, adhesion to collagen increased activation of focal adhesion kinase (FAK), c-Src, and ERK and facilitated survival (prevented apoptosis). GEC on plastic exhibited increased caspase-8 and -9 activities, increased expression of the proapoptotic protein, Bax, and decreased the antiapoptotic protein, Bcl-XL, compared with collagen. Stable expression of constitutively active mutants of FAK (CD2-FAK) or MEK (R4F-MEK) activated the ERK pathway and supplanted the requirement of collagen for survival. In contrast, expression of a Ras mutant that activates phosphatidylinositol 3-kinase but blocks ERK activation or pharmacological inhibition of the ERK pathway decreased survival on collagen. Glomeruli isolated from rats with PAN revealed increased beta1-integrin expression, along with increased activation of FAK, c-Src, and ERK, compared with controls. EGF receptor activation was undetectable in PAN. Therefore, adhesion to collagen, resulting in activation of FAK and the Ras-ERK pathway, supports GEC survival. Analogous signals for GEC survival are activated in PAN.
机译：肾小球上皮细胞（GEC）的损伤和凋亡可能导致肾小球肾炎的硬化。本研究解决了调节GEC在培养中和体内GEC损伤的急性嘌呤霉素氨基核苷酸肾病（PAN）模型中的信号。与塑料基质上的GEC相比，对胶原蛋白的粘附增加了粘着斑激酶（FAK），c-Src和ERK的活化并促进了存活（预防了细胞凋亡）。与胶原蛋白相比，塑料上的GEC表现出增加的caspase-8和-9活性，增加了促凋亡蛋白Bax的表达，并降低了抗凋亡蛋白Bcl-XL。 FAK（CD2-FAK）或MEK（R4F-MEK）的组成型活性突变体的稳定表达激活了ERK途径，并取代了生存所需的胶原蛋白。相反，激活磷脂酰肌醇3激酶但阻断ERK激活或ERK途径的药理学抑制作用的Ras突变体的表达降低了胶原蛋白的存活率。与对照组相比，从患有PAN的大鼠中分离出的肾小球显示出β1-整合素的表达增加，以及FAK，c-Src和ERK的激活增加。在PAN中无法检测到EGF受体激活。因此，与胶原蛋白的粘附导致FAK和Ras-ERK途径的激活，支持GEC生存。在PAN中激活GEC生存的类似信号。

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