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

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.

DOI: 10.1159/000312883

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@article{Sakamaki2010AbsenceOG, title={Absence of gelatinase (MMP-9) or collagenase (MMP-13) attenuates adriamycin-induced albuminuria and glomerulosclerosis.}, author={Yusuke Sakamaki and Hiroyuki Sasamura and Kaori Hayashi and Kimiko Ishiguro and Hironari Takaishi and Yasunori Okada and Jeanine M D'armiento and Takao Saruta and Hiroshi Itoh}, journal={Nephron. Experimental nephrology}, year={2010}, volume={115 2}, pages={e22-32} }