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Effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells.
Chin Med J (Engl). 2007 Nov 05; 120(21):1886-9.CM

Abstract

BACKGROUND

The decreased degradation of extra-cellular matrix proteins plays an important role in the onset of diabetic nephropathy. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), which are members of the matrix metalloproteinase family, are associated with this process. Angiotensin II (AII) plays an important role in the development of diabetic nephropathy also. This research aimed to investigate the effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of MMP-9 and TIMP-1 in rat mesangial cells.

METHODS

Rat mesangial cells were cultured and divided into 5 groups: normal glucose (group NG), high glucose (group HG), group NG + AII, NG + AII + saralasin (group NG + AII + S, saralasin is the AII receptor blocker) and HG + saralasin (group HG + S). After the cells were incubated for 24 hours, AII concentrations in the supernatant were measured by radioimmunoassay and the expression of MMP-9 and TIMP-1 mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS

AII concentrations were higher in group HG ((56.90 +/- 13.54) pg/ml) and group HG + S ((51.30 +/- 5.96) pg/ml) than in group NG ((37.89 +/- 8.62) pg/ml, P < 0.05), whereas there was no significant difference between group HG and group HG + S. The expression of MMP-9 mRNA and MMP-9/TIMP-1 mRNA ratio in group NG + AII (MMP-9, 0.33 +/- 0.04; MMP-9/TIMP-1, 0.40 +/- 0.06) and group HG (MMP-9, 0.36 +/- 0.02; MMP-9/TIMP-1, 0.45 +/- 0.03) were decreased more significantly than those in group NG (MMP-9, 0.72 +/- 0.02; MMP-9/TIMP-1, 1.21 +/- 0.07). These values in group NG + AII + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.18 +/- 0.05) were higher than those in group NG + AII, and the values in group HG + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.16 +/- 0.05) were higher than those in group HG (all were P < 0.05). TIMP-1 mRNA expression was increased more significantly in group NG + AII (0.81 +/- 0.03) and group HG (0.80 +/- 0.03) than in group NG (0.59 +/- 0.02), but it was lower in group NG + AII + S (0.60 +/- 0.01) than in group NG + AII and also lower in group HG + S (0.61 +/- 0.01) than in group HG (all were P < 0.05).

CONCLUSIONS

High glucose stimulates AII production. Both high glucose and AII induce a decrease in MMP-9 mRNA expression and MMP-9/TIMP-1 mRNA ratio as well as an increase in TIMP-1 mRNA expression, which can be reversed by saralasin, suggesting that high glucose can aggravate impaired matrix degradation by altering gene expression of MMP-9 and TIMP-1 and that the effect of high glucose may be mediated by AII.

Authors+Show Affiliations

Department of Endocrinology, Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. helinding@tom.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18067760

Citation

Ding, He-lin, et al. "Effect of Angiotensin II Receptor Blocker On Glucose-induced mRNA Expressions of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Rat Mesangial Cells." Chinese Medical Journal, vol. 120, no. 21, 2007, pp. 1886-9.
Ding HL, Guo Y, Xu MT, et al. Effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells. Chin Med J (Engl). 2007;120(21):1886-9.
Ding, H. L., Guo, Y., Xu, M. T., Li, H. Y., & Fu, Z. Z. (2007). Effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells. Chinese Medical Journal, 120(21), 1886-9.
Ding HL, et al. Effect of Angiotensin II Receptor Blocker On Glucose-induced mRNA Expressions of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Rat Mesangial Cells. Chin Med J (Engl). 2007 Nov 5;120(21):1886-9. PubMed PMID: 18067760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells. AU - Ding,He-lin, AU - Guo,Ying, AU - Xu,Ming-tong, AU - Li,Hai-yan, AU - Fu,Zu-zhi, PY - 2007/12/11/pubmed PY - 2008/9/23/medline PY - 2007/12/11/entrez SP - 1886 EP - 9 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 120 IS - 21 N2 - BACKGROUND: The decreased degradation of extra-cellular matrix proteins plays an important role in the onset of diabetic nephropathy. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), which are members of the matrix metalloproteinase family, are associated with this process. Angiotensin II (AII) plays an important role in the development of diabetic nephropathy also. This research aimed to investigate the effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of MMP-9 and TIMP-1 in rat mesangial cells. METHODS: Rat mesangial cells were cultured and divided into 5 groups: normal glucose (group NG), high glucose (group HG), group NG + AII, NG + AII + saralasin (group NG + AII + S, saralasin is the AII receptor blocker) and HG + saralasin (group HG + S). After the cells were incubated for 24 hours, AII concentrations in the supernatant were measured by radioimmunoassay and the expression of MMP-9 and TIMP-1 mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AII concentrations were higher in group HG ((56.90 +/- 13.54) pg/ml) and group HG + S ((51.30 +/- 5.96) pg/ml) than in group NG ((37.89 +/- 8.62) pg/ml, P < 0.05), whereas there was no significant difference between group HG and group HG + S. The expression of MMP-9 mRNA and MMP-9/TIMP-1 mRNA ratio in group NG + AII (MMP-9, 0.33 +/- 0.04; MMP-9/TIMP-1, 0.40 +/- 0.06) and group HG (MMP-9, 0.36 +/- 0.02; MMP-9/TIMP-1, 0.45 +/- 0.03) were decreased more significantly than those in group NG (MMP-9, 0.72 +/- 0.02; MMP-9/TIMP-1, 1.21 +/- 0.07). These values in group NG + AII + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.18 +/- 0.05) were higher than those in group NG + AII, and the values in group HG + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.16 +/- 0.05) were higher than those in group HG (all were P < 0.05). TIMP-1 mRNA expression was increased more significantly in group NG + AII (0.81 +/- 0.03) and group HG (0.80 +/- 0.03) than in group NG (0.59 +/- 0.02), but it was lower in group NG + AII + S (0.60 +/- 0.01) than in group NG + AII and also lower in group HG + S (0.61 +/- 0.01) than in group HG (all were P < 0.05). CONCLUSIONS: High glucose stimulates AII production. Both high glucose and AII induce a decrease in MMP-9 mRNA expression and MMP-9/TIMP-1 mRNA ratio as well as an increase in TIMP-1 mRNA expression, which can be reversed by saralasin, suggesting that high glucose can aggravate impaired matrix degradation by altering gene expression of MMP-9 and TIMP-1 and that the effect of high glucose may be mediated by AII. SN - 0366-6999 UR - https://www.unboundmedicine.com/medline/citation/18067760/Effect_of_angiotensin_II_receptor_blocker_on_glucose_induced_mRNA_expressions_of_matrix_metalloproteinase_9_and_tissue_inhibitor_of_metalloproteinase_1_in_rat_mesangial_cells_ L2 - https://Insights.ovid.com/pubmed?pmid=18067760 DB - PRIME DP - Unbound Medicine ER -