Renin angiotensin system and different mediators induce renal fibrosis

Renal fibrosis (RF) is the final step in chronic kidney disease (CKD) that is represented by abundant extracellular matrix (ECM) components, tubular atrophy and inflammatory cell infiltration. Renal failure results from a series of factors as follows; the activation of cytokines due to the entrance of bioactive molecules of plasma to the tubulointerstitial space, the activation of signal molecules such as transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), the activation of renin angiotensin system (RAS) especially angiotensin II (Ang II), endothelin-۱, other pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-۱ (IL-۱), and finally endothelial to mesenchymal transition. Among all factors, this review focuses on RAS by considering the role of component of two axes of this system and mediators involved in RF. Ang II participates in many chronic diseases such as hypertension and chronic heart disease. Moreover, ACE/Ang II/ATR axis exhibits a fibrogenic effect while angiotensin (۱-۷) reveals both anti-fibrotic and fibrotic effects. However, most researchers believe in the renoprotective effect of ACE۲/Ang ۱-۷/MasR axis. The ratios of activities of these two axes determine the progression or inhibition of RF. Several signaling pathways and cytokines play role in RF but TGF-β is the most important mediator. The existence of a feedback relationship between TGF-β and RAS is considered in this study.

کلیدواژه ها:

Renal fibrosis ، Renin angiotensin system ، Angiotensin II ، Angiotensin (۱-۷) ، pro-inflammatory cytokines