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  • Title: Tetrahydrobiopterin contributes to the proliferation of mesangial cells and accumulation of extracellular matrix in early-stage diabetic nephropathy.
    Author: Wang J, Yang Q, Nie Y, Guo H, Zhang F, Zhou X, Yin X.
    Journal: J Pharm Pharmacol; 2017 Feb; 69(2):182-190. PubMed ID: 28033650.
    Abstract:
    OBJECTIVES: Nitric oxide (NO) plays an important role in the progression of early-stage diabetic nephropathy (DN), which is found to contribute to extracellular matrix (ECM) accumulation in mesangial cells (MCs). As a cofactor for NO production, tetrahydrobiopterin (BH4 ), a folacin analogue, may be responsible for the ECM accumulation and proliferation of MCs. This study was to investigate the effects of BH4 on glomerulosclerosis in early-stage DN. METHODS: In in vitro studies with cultured mesangial cells and in vivo studies with streptozotocin-induced diabetic rats, BH4 levels were assayed by HPLC; NO was determined by Griess agents; laminin and collagen IV were determined by enzyme-linked immunosorbent assay; the inducible NO synthase protein was determined by immunofluorescence staining and Western blot; and mesangial matrix expansion and MC proliferation in the renal cortex were observed by periodic acid-schiff staining and transmission electron microscopy, respectively. KEY FINDINGS: The in vivo and in vitro studies indicated that the increased BH4 resulted in the overproduction of NO, ECM accumulation and the proliferation of MCs in early-stage DN. CONCLUSIONS: Our results suggest that inhibiting excessive BH4 may be a potential approach to prevent glomerulosclerosis in early-stage DN.
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