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.