title: Tetrahydrobiopterin contributes to the proliferation of mesangial cells and accumulation of extracellular matrix in early-stage diabetic nephropathy.
abstract: OBJECTIVE
  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 BH4on glomerulosclerosis in early-stage DN.
  
  
  METHODS
  In in vitro studies with cultured mesangial cells and in vivo studies with streptozotocin-induced diabetic rats, BH4levels 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.
  
  
  RESULTS
  The in vivo and in vitro studies indicated that the increased BH4resulted in the overproduction of NO, ECM accumulation and the proliferation of MCs in early-stage DN.
  
  
  CONCLUSIONS
  Our results suggest that inhibiting excessive BH4may be a potential approach to prevent glomerulosclerosis in early-stage DN.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D007797:Laminin / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D013400:Sugar Acids / Q000494:pharmacology
chemical_list: C017182:5-dehydro-3-deoxy-D-arabino-heptulosonic acid-7-phosphate; D007797:Laminin; D013400:Sugar Acids; D001708:Biopterins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C003402:sapropterin
keywords: diabetic nephropathy; extracellular matrix; nitric oxide; proliferation; tetrahydrobiopterin