| First Author | Bylander J | Year | 2008 |
| Journal | Am J Physiol Renal Physiol | Volume | 294 |
| Issue | 3 | Pages | F480-90 |
| PubMed ID | 18172000 | Mgi Jnum | J:132021 |
| Mgi Id | MGI:3774964 | Doi | 10.1152/ajprenal.00214.2007 |
| Citation | Bylander J, et al. (2008) Targeted disruption of the meprin metalloproteinase {beta} gene protects against renal ischemia-reperfusion injury in mice. Am J Physiol Renal Physiol 294(3):F480-90 |
| abstractText | Meprins are membrane-bound and secreted metalloproteinases consisting of alpha- and/or beta-subunits that are highly expressed in mouse kidney proximal tubules. Previous studies have implied that the meprin alpha/beta-isoform is deleterious when renal tissue is subjected to ischemia-reperfusion (I/R). To delineate the roles of the meprin isoforms in renal disease, we subjected mice deficient in meprin-beta (KO) and their wild-type (WT) counterparts to I/R. WT mice were markedly more susceptible to renal injury after I/R than the meprin-beta KO mice as determined by blood urea nitrogen levels. Urinary levels of inflammatory cytokines IL-6 and KC (CXCL1) were significantly higher in WT compared with meprin-beta KO mice by 6 h post-I/R. At 96 h postischemia, kidney mRNA expression levels for tumor necrosis factor-alpha, transforming growth factor-beta, inducible nitric oxide synthase, and heat shock protein-27 were significantly higher in the WT than meprin-beta KO mice. For WT mice subjected to I/R, there was a rapid (3 h) redistribution of meprin beta-subunits in cells in S3 segments of proximal tubules, followed by shedding of apical cell membrane and detachment of cells. These studies indicate that meprin-beta is important in the pathogenesis of renal injury following I/R and that the redistribution of active meprin-alpha/beta is a major contributor to renal injury and subsequent inflammation. |
