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Effect of a specific endothelin receptor A antagonist and an angiotensin-converting enzyme inhibitor on glomerular mRNA levels for extracellular matrix components, metalloproteinases (MMP) and a tissue inhibitor of MMP in aminonucleoside nephrosis.
Nephrol Dial Transplant. 1997 May; 12(5):1001-6.ND

Abstract

BACKGROUND

We previously reported that mRNA levels for extracellular matrix (ECM) components and endothelin (ET)-1 are upregulated in glomeruli of puromycin aminonucleoside (PAN) nephrosis. Angiotensin-converting enzyme (ACE) inhibitors are effective in experimental models of renal injury, including PAN nephrosis. This study was designed to assess whether the glomerular expression of mRNA for ECM components, ET-1, metalloproteinases (MMP), and a tissue inhibitor of metalloproteinases (TIMP) is modulated by a specific endothelin receptor A antagonist (FR139317) or angiotensin-converting enzyme inhibitor (enalapril) in PAN-injected rats.

METHODS

Animals were divided into six groups. Group 1 consisted of PAN-injected rats given no treatment. In group 2, PAN-injected rats were given enalapril 35 mg/l. In group 3, PAN-injected rats were given an intraperitoneal injection of FR139317. Group 4 consisted of saline-injected rats given no treatment. In group 5, saline-injected rats were given enalapril. In group 6, saline-injected rats were given FR139317. We prepared glomerular RNA and performed Northern blot analysis in all groups.

RESULTS

In PAN nephrosis, glomerular mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, ET-1, MMP-2 and TIMP-1 increased at the peak of proteinuria on day 8 and then decreased to the control level by day 20, whereas those for alpha 1 (I) and alpha 1 (III) collagen chains, MMP-1, MMP-3 and GAPDH showed little change in PAN nephrosis throughout the experimental periods. In contrast, mRNA levels for heparan sulphate proteoglycan (HSPG) decreased on day 8 and then increased to the control level by day 20. Both enalapril and FR139317 attenuated the increases in mRNA levels for alpha 1 (IV) collagen chain (P < 0.01), laminin chains (P < 0.01), and ET-1 (P < 0.01), and attenuated the decreases in mRNA levels for HSPG (P < 0.01) in glomeruli of PAN-injected rats. Enalapril had little effect on increased glomerular mRNA levels for MMP-2 and TIMP-1 in PAN nephrosis, whereas FR139317 attenuated the increases in glomerular mRNA levels for MMP-2 (P < 0.01) and TIMP-1 (P < 0.01).

CONCLUSIONS

These data suggest that the beneficial effects of enalapril and FR139317 may be related to modulation of glomerular mRNA expression of ECM components and ET-1 and that these agents may follow a different mechanism in regulating the glomerular mRNA expression for MMP-2 and TIMP-1 in PAN nephrosis.

Authors+Show Affiliations

Department of Medicine, Koto Hospital, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9175058

Citation

Ebihara, I, et al. "Effect of a Specific Endothelin Receptor a Antagonist and an Angiotensin-converting Enzyme Inhibitor On Glomerular mRNA Levels for Extracellular Matrix Components, Metalloproteinases (MMP) and a Tissue Inhibitor of MMP in Aminonucleoside Nephrosis." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 12, no. 5, 1997, pp. 1001-6.
Ebihara I, Nakamura T, Tomino Y, et al. Effect of a specific endothelin receptor A antagonist and an angiotensin-converting enzyme inhibitor on glomerular mRNA levels for extracellular matrix components, metalloproteinases (MMP) and a tissue inhibitor of MMP in aminonucleoside nephrosis. Nephrol Dial Transplant. 1997;12(5):1001-6.
Ebihara, I., Nakamura, T., Tomino, Y., & Koide, H. (1997). Effect of a specific endothelin receptor A antagonist and an angiotensin-converting enzyme inhibitor on glomerular mRNA levels for extracellular matrix components, metalloproteinases (MMP) and a tissue inhibitor of MMP in aminonucleoside nephrosis. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 12(5), 1001-6.
Ebihara I, et al. Effect of a Specific Endothelin Receptor a Antagonist and an Angiotensin-converting Enzyme Inhibitor On Glomerular mRNA Levels for Extracellular Matrix Components, Metalloproteinases (MMP) and a Tissue Inhibitor of MMP in Aminonucleoside Nephrosis. Nephrol Dial Transplant. 1997;12(5):1001-6. PubMed PMID: 9175058.
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TY - JOUR T1 - Effect of a specific endothelin receptor A antagonist and an angiotensin-converting enzyme inhibitor on glomerular mRNA levels for extracellular matrix components, metalloproteinases (MMP) and a tissue inhibitor of MMP in aminonucleoside nephrosis. AU - Ebihara,I, AU - Nakamura,T, AU - Tomino,Y, AU - Koide,H, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez SP - 1001 EP - 6 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 12 IS - 5 N2 - BACKGROUND: We previously reported that mRNA levels for extracellular matrix (ECM) components and endothelin (ET)-1 are upregulated in glomeruli of puromycin aminonucleoside (PAN) nephrosis. Angiotensin-converting enzyme (ACE) inhibitors are effective in experimental models of renal injury, including PAN nephrosis. This study was designed to assess whether the glomerular expression of mRNA for ECM components, ET-1, metalloproteinases (MMP), and a tissue inhibitor of metalloproteinases (TIMP) is modulated by a specific endothelin receptor A antagonist (FR139317) or angiotensin-converting enzyme inhibitor (enalapril) in PAN-injected rats. METHODS: Animals were divided into six groups. Group 1 consisted of PAN-injected rats given no treatment. In group 2, PAN-injected rats were given enalapril 35 mg/l. In group 3, PAN-injected rats were given an intraperitoneal injection of FR139317. Group 4 consisted of saline-injected rats given no treatment. In group 5, saline-injected rats were given enalapril. In group 6, saline-injected rats were given FR139317. We prepared glomerular RNA and performed Northern blot analysis in all groups. RESULTS: In PAN nephrosis, glomerular mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, ET-1, MMP-2 and TIMP-1 increased at the peak of proteinuria on day 8 and then decreased to the control level by day 20, whereas those for alpha 1 (I) and alpha 1 (III) collagen chains, MMP-1, MMP-3 and GAPDH showed little change in PAN nephrosis throughout the experimental periods. In contrast, mRNA levels for heparan sulphate proteoglycan (HSPG) decreased on day 8 and then increased to the control level by day 20. Both enalapril and FR139317 attenuated the increases in mRNA levels for alpha 1 (IV) collagen chain (P < 0.01), laminin chains (P < 0.01), and ET-1 (P < 0.01), and attenuated the decreases in mRNA levels for HSPG (P < 0.01) in glomeruli of PAN-injected rats. Enalapril had little effect on increased glomerular mRNA levels for MMP-2 and TIMP-1 in PAN nephrosis, whereas FR139317 attenuated the increases in glomerular mRNA levels for MMP-2 (P < 0.01) and TIMP-1 (P < 0.01). CONCLUSIONS: These data suggest that the beneficial effects of enalapril and FR139317 may be related to modulation of glomerular mRNA expression of ECM components and ET-1 and that these agents may follow a different mechanism in regulating the glomerular mRNA expression for MMP-2 and TIMP-1 in PAN nephrosis. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/9175058/Effect_of_a_specific_endothelin_receptor_A_antagonist_and_an_angiotensin_converting_enzyme_inhibitor_on_glomerular_mRNA_levels_for_extracellular_matrix_components_metalloproteinases__MMP__and_a_tissue_inhibitor_of_MMP_in_aminonucleoside_nephrosis_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/12.5.1001 DB - PRIME DP - Unbound Medicine ER -