TGF-b/Smad, integrin-linked kinase, and Wnt/b-catenin signaling are essential intracellular signal transduction pathways for controlling the process of EMT. TGF-b1 is the most potent factor for EMT, and many other prosclerotic factors have indirect effects on EMT, via the induction of TGF-b1. RAAS activation is able to induce EMT by both TGF-dependent and Benzoylaconine TGF-independent actions. Angiotensin II mediates EMT in tubular cells by activating ANG 1�C7/MAS-1-dependent pathways. Our results show that IS and PCS could induce EMT in tubular cells in vitro and in vivo, and activation of the TGF-b/Smad pathway by RAAS is a possible mechanism. Our study also shows that IS and PCS could increase the expression of the 4EGI-1 EMT-associated transcription factor Snail in renal tubules. Snail has been reported to be a key effector in cancer-related EMT, which is associated with malignant tumor progression. The interaction between the Snail and TGF-b signaling pathway is mutual. It was reported that TGF-b1 hyperexpression could increase Snail expression. Previous studies have showed that Snail was a key mediator in the TGFb1-mediated EMT. Blocking Snail function could mitigate the TGF-b1-mediated EMT. In breast cancer, Snail and Slug could activate TGF-b signaling pathway. Snail induction by adriamycin is also known to cause mesenchymal conversion of podocytes. A previous study with obstructive nephropathy animal model revealed that blocking RAAS with angiotensin II receptor, renin receptor blockers or both could decrease the Snail-1 and TGF-b1 expression, and attenuated UUO-related kidney fibrosis. Our study also showed similar results. It was suggested that an increase in Snail expression as a result of TGF-b pathway activation has an important role in the EMT process induced by IS and PCS in renal tubular cells. The putative mechanisms for the kidney fibrosis induced by IS and PCS was summarized in Figure 9. The activation of the renal RAAS/TGF-b pathway has an important pathological role in chronic kidney injury caused by IS and PCS. IS and PCS may increase Snail expression which might further increase TGF-b expression, and induce EMT-like transition in renal tubular cells. Our study details the pathological mechanisms of chronic renal injury caused by uremic toxins. However, it should be stressed that this study has some limitations because only a mouse model and a cultured mouse renal tubular cell line were used. Whether these results can extend to primary culture renal tubular cells, and be applied to human disease, remains to be determined. Understanding biodiversity is fundamental to ecological research and key to maintaining a healthy environment and a sustainable economy. However, biodiversity science remains the study of unknowns.Therefore, not only is our characterization of biodiversity painstakingly slow, but the fact that there is order-of-magnitude uncertainty in our best estimate for the totality of Earth��s biodiversity suggests that current tools and techniques are inadequate for the task of accurate assessment. Both questions are difficult to answer in a consistent and timely fashion, and nearly impossible to implement as monitoring objectives.