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.
Keywords: Complement 3; Epithelial-to-mesenchymal transition; Hypertension Mesenchymal cell; Spontaneously hypertensive rat.