Unconjugated
In this work, we demonstrated for the first time that S-propargyl-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide (H2S)-releasing compound, had renoprotective effects on streptozotocin (STZ)-induced diabetic kidney injury. SPRC treatment significantly reduced the level of creatinine, kidney to body weight ratio and in particular, markedly decreased 24-h urine microalbuminuria excretion. SPRC suppressed the mRNA expression of fibronectin and type IV collagen. In vitro, SPRC inhibited mesangial cells over-proliferation and hypertrophy induced by high glucose. Additionally, SPRC attenuated inflammation in diabetic kidneys. SPRC also reduced transforming growth factor β1 (TGF-β1) signaling and expression of phosphorylated Smad3 (p-Smad3) pathway. Moreover, SPRC inhibited phosphorylation of ERK, p38 protein. Taken together, SPRC was demonstrated to be a potential therapeutic candidate to suppress diabetic nephropathy.
This study was designed to investigate the effect of recombinant sTGFβ1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and the expression of SMAD3 and STAT6. The proteins sTGFβ1RII and sIL13Rα2 were expressed in Escherichiacoli, purified using affinity chromatography and characterized by Western blotting. Female BALB/C mice (48) were randomly divided into eight groups and infected with Schistosoma japonicum. Five weeks after infection, test groups were injected with the recombinant proteins at different doses. Eight weeks after infection, lung and hepatic tissue samples were obtained and stained with hematoxylin and eosin (HE) and Masson's trichrome. Immunohistochemical staining was used to detect the expression of SMAD3 and STAT6. The recombinant proteins sTGFβ1RII and sIL13Rα2 were successfully expressed, purified, and characterized. The granuloma area, hepatic hydroxyproline (HYP) level and hepatic fibrosis of the protein therapeutic groups were significantly smaller than those of the positive control group (P<0.01). Treatment with sTGFβ1RII was more effective when the protein was administered for 4weeks rather than 2 (P<0.01). Hepatic fibrosis in the groups using a low dose of protein sTGFβ1 was lower that of the combination group (P<0.05). The expression level of STAT6 was significantly lower in groups treated with sIL13Rα2 than in groups not treated with the protein (P<0.01). The recombinant proteins TGFβ1RII and sIL13Rα2 were able to decrease granuloma area and hepatic fibrosis in schistosomiasis japonica, and also reduced the expression of the signal transduction proteins SMAD3 and STAT6. The proteins were more effective when used in combination than when applied singly.