FIGURE 4.

The diagrammatic illustration of the influence of H₂S on the mechanisms involved in the initiation and development of renal diseases. H₂S suppresses the elevation of Hcy resulting in the downregulation of proinflammatory cytokines (such as IL-1β, IL-6, and NF-қB) and the corresponding reduction of proinflammatory activities. Moreover, H₂S increases the expressions of 20S proteasome which then reduces the oxidation of proteins by mediating proteolytic degradation of the oxidized proteins. Next, H₂S can also stimulate the oxidation of GSH to GSSG resulting in the reduction of free oxygen radicals and subsequent suppression of protein oxidation. By reducing free oxygen radicals level, H₂S also prevents the oxidations of Trx and its binding into TXNIP resulting in reduction of cell injury. Next, H₂S prevents the ROS-mediated activation of AMPK pathway and its downstream effect on the induction of autophagy. Similarly, H₂S reduces the expressions of MMPs and their resulting effects in EMT and matrix production. Also, H₂S suppresses the levels of TRPC-6 leading to a reduction in cell injury. Alternatively, the decline in H₂S levels could reverse the protective effects, resulting in the promotion of mechanisms favoring the development of kidney diseases (H₂S, hydrogen sulfide; Hcy, homocysteine; GSH, glutathione; GSSG, oxidized glutathione; ROS, reactive oxygen species; TRPC-6, transient receptor potential cation channel, subfamily C, member 6; MMPs, matrix metalloproteinases; EMT, epithelial-mesenchymal transition; Trx, thioredoxin; TXNIP, Trx-interacting protein; AMPK, AMP-activated protein kinase).