title: C-peptide exhibits a late induction effect on matrix metallopeptidase-9 in high glucose-stimulated rat mesangial cells.
abstract: Insufficient matrix metalloproteinase (MMP)-9 and MMP-2 is considered to be a contributor of extracellular matrix (ECM) accumulation in diabetic nephropathy (DN). C-peptide can reverse fibrosis, thus exerting a beneficial effect on DN. Whether C-peptide induces MMP-9 and MMP-2 to reverse ECM accumulation is not clear. In the present study, in order to determine ECM metabolism, rat mesangial cells were treated with high glucose (HG) and C-peptide intervention, then the early and late effects of C-peptide on HG-affected MMP-9 and MMP-2 were evaluated. Firstly, it was confirmed that HG mainly suppressed MMP-9 expression levels. Furthermore, C-peptide treatment induced MMP-9 expression at 6 h and suppressed it at 24 h, revealing the early dual effects of C-peptide on MMP-9 expression. Subsequently, significant increase in MMP-9 expression at 72, 96 and 120 h C-peptide treatment was observed. These changes in MMP-9 protein content confirmed its expression changes following late C-peptide treatment. Furthermore, at 96 and 120 h C-peptide treatment reversed the HG-inhibited MMP-9 secretion, further indicating the late induction effect of C-peptide on MMP-9. The present results demonstrated that C-peptide exerted a late induction effect on MMP-9 in HG-stimulated rat mesangial cells, which may be associated with the underlying mechanism of C-peptide's reversal effects on DN.
authors.affiliation: Department of Molecular Biology, Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Molecular Biology, Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Molecular Biology, Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Kunyu
authors.initials: K
authors.lastname: He
keywords: C-peptide; diabetic nephropathy; extracellular matrix; matrix metalloproteinase-2; matrix metalloproteinase-9