Absence of gelatinase (MMP-9) or collagenase (MMP-13) attenuates adriamycin-Induced albuminuria and glomerulosclerosis

Yusuke Sakamaki, Hiroyuki Sasamura, Kaori Hayashi, Kimiko Ishiguro, Hironari Takaishi, Yasunori Okada, Jeanine M. D'Armiento, Takao Saruta, Hiroshi Itoh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background/Aims: The role of matrix metalloproteinases (MMPs) in the pathogenesis of glomerular injury appears to be complex. To investigate the role of individual MMPs, we examined the course of Adriamycin-induced albuminuria and glomerulosclerosis in mice lacking either a gelatinase (MMP-9) or a collagenase (MMP-13). Methods: Adriamycin was administered to MMP-9 or MMP-13 knockout (KO) mice. Glomerular injury was assessed by the quantification of albuminuria, the glomerular injury score and type IV collagen immunostaining. Results: Treatment of mice with Adriamycin (18 mg/kg i.v.) resulted in marked albuminuria and glomerulosclerosis reaching a peak at 4-8 weeks. The albuminuria and glomerulosclerosis were significantly (p < 0.05) attenuated in both the MMP-9 KO and MMP-13 KO mice compared to controls. In contrast, treatment of wild-type mice with the broad-spectrum MMP inhibitor doxycycline did not have a beneficial effect on the albuminuria and glomerulosclerosis. Conclusion: These results support a role for both gelatinase (MMP-9) and collagenase (MMP-13) in the pathogenesis of glomerular injury in the Adriamycin-induced glomerulosclerosis model. MMP inhibitors with high specificity towards MMP-9 and/or MMP-13 may be potential future candidates to provide more effective therapies to inhibit the development of glomerulosclerosis.

Original languageEnglish
Pages (from-to)e22-e32
JournalNephron - Experimental Nephrology
Volume115
Issue number2
DOIs
Publication statusPublished - 2010 Jun 1

Keywords

  • Adriamycin
  • Glomerulosclerosis
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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