The effects of taurine on extracellular matrix proteins in A diabetic nephropathy model and investigation of associated signaling pathways

Diabetic nephropathy (DN), the cause of end-stage renal disease, is characterized by morphological and structural changes in the kidney due to the accumulation of extracellular matrix (ECM). One of the most important causes of this accumulation is oxidative stress. Taurine, a semi-essential amino acid, has antioxidant and antifibrotic properties. This study aimed to investigate the possible renoprotective effects of taurine via p38 MAPK and TGF-β/smad2/3 signaling pathways in a diabetic nephropathy model in rats. In our study, 29 Wistar albino rats were divided into 4 groups: control, taurine (1% with drinking water), diabetes (45 mg/kg Streptozotosin), diabetes+taurine. After 12 weeks, kidney and serum were collected for biochemical and histological studies. The histological analysis showed that there were significant changes in tubule dilatation and loss of tubule brush border in the kidney of the diabetes group. These changes were significantly decreased with taurine. However, there were no significant changes in serum creatinine and blood urine nitrogen levels among the groups. Further, taurine significantly reduced the protein expression of NADPH oxidase 4 (NOX4), known as a major enzymatic source of oxidative stress in the kidney. Also, there was a significant decrease in reactive oxygen species and malondialdehyde levels by taurine whereas the decreased SOD activity level in the diabetes group was significantly increased with taurine. On the other hand, taurine resulted in significant decreases in both mRNA and protein expression of fibronectin, which is a major extracellular matrix protein related to the fibrosis process, These findings were parallel to Masson Trichrome staining. The matrix metalloproteinases (MMP)-2 and MMP-9 mRNA expression levels and their activities increased significantly in diabetes compared to the control, and these increases were significantly reached higher levels with taurine. Also, the decreased mRNA expression of extracellular matrix metalloproteinase inducer (EMMPRIN) increased with taurine in the diabetes+taurine group. Moreover, it was found that taurine suppressed the p38 MAPK and TGF-β/smad2/3 signaling pathways. These findings indicate that taurine may be an effective practical strategy to prevent renal diabetic injury.