The complement system has recently been reported to contribute to the development and pathogenesis of hypertension, several cardiovascular and renal diseases, and cardiometabolic disorders accompanied by inflammation and tissue remodeling. We have demonstrated that complement 3 (C3) is highly expressed in mesenchymal tissues in spontaneously hypertensive rats (SHRs) and induces the synthetic phenotype and exaggerated growth of mesenchymal cells by maintenance effect on dedifferentiated cells. To verify the role of C3 in the pathogenesis of hypertension, we targeted the C3 gene from SHRs by zinc-finger nuclease gene-editing technology and demonstrated that the increased expression of C3 induces salt-sensitive hypertension with activation of the renal renin-angiotensin system in SHRs. We recently found that increased expression of C3 is associated with the suppression of miR145 and induces Krüppel-like factor 5 and the synthetic phenotype of mesenchymal cells in SHRs. We also demonstrated that C3 is involved in the epithelial-to-mesenchymal transition and dedifferentiation of epithelial cells in kidneys subjected to unilateral ureteral obstruction with elevation of blood pressure. Thus, C3 is an essential factor in the pathogenesis of hypertension due to its maintenance effect on undifferentiated mesenchymal cells.

中文翻译：

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补体3在高血压发病机制中的作用

最近有报道称补体系统有助于高血压、几种心血管和肾脏疾病以及伴有炎症和组织重塑的心脏代谢紊乱的发展和发病机制。我们已经证明补体 3 (C3) 在自发性高血压大鼠 (SHR) 的间充质组织中高度表达，并通过对去分化细胞的维持作用诱导间充质细胞的合成表型和过度生长。为了验证 C3 在高血压发病机制中的作用，我们通过锌指核酸酶基因编辑技术靶向 SHR 中的 C3 基因，并证明 C3 表达的增加会通过激活肾肾素 - 血管紧张素系统诱导盐敏感性高血压在 SHR 中。我们最近发现 C3 表达的增加与 miR145 的抑制有关，并诱导 Krüppel 样因子 5 和 SHR 中间充质细胞的合成表型。我们还证明，C3 参与单侧输尿管梗阻伴血压升高的肾脏上皮细胞向间充质转化和去分化。因此，由于其对未分化间充质细胞的维持作用，C3 是高血压发病机制中的重要因素。我们还证明，C3 参与单侧输尿管梗阻伴血压升高的肾脏上皮细胞向间充质转化和去分化。因此，由于其对未分化间充质细胞的维持作用，C3 是高血压发病机制中的重要因素。我们还证明，C3 参与单侧输尿管梗阻伴血压升高的肾脏上皮细胞向间充质转化和去分化。因此，由于其对未分化间充质细胞的维持作用，C3 是高血压发病机制中的重要因素。