The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease

• Published in: Kidney research and clinical practice Vol. 37; no. 3; pp. 222 - 229
• Main Authors: Rhee, Harin, Han, Miyeun, Kim, Sang Soo, Kim, Il Young, Lee, Hye Won, Bae, Sun Sik, Ha, Hong Koo, Jung, Eun Soon, Lee, Min Young, Seong, Eun Young, Lee, Dong Won, Lee, Soo Bong, Lovett, David H, Song, Sang Heon
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Nephrology 01.09.2018; The Korean Society of Nephrology; 대한신장학회
• Subjects: Aging; Chronic renal insufficiency; Diabetes mellitus; Matrix metalloproteinase-2; Original; 내과학; Aging; Chronic renal insufficiency; Diabetes mellitus; Matrix metalloproteinase-2
• ISSN: 2211-9132; 2211-9140
• DOI: 10.23876/j.krcp.2018.37.3.222

This study was undertaken to explore the effects of aging on the kidneys in mouse models of diabetes and chronic kidney disease (CKD), and to compare the expression of two isoforms of matrix metalloproteinase-2 (MMP-2)-secretory full-length MMP-2 and intracellular N-terminal truncated MMP-2 (NTT-MMP-2)-in these models. Two experimental ICR mouse models were used: a streptozotocin (STZ)-induced type 1 diabetes mellitus model and a 5/6 nephrectomized (5/6Nx) CKD model. The abundance of each isoform of MMP-2 was determined by quantitative polymerase chain reaction (qPCR), and functional analyses were conducted. Moreover, the protein levels of the two MMP-2 isoforms were determined semi-quantitatively by immunohistochemical staining, and their association with tissue damage was assessed. Both isoforms of MMP-2 were upregulated in the kidney tissues of STZ-induced diabetic mice and 5/6Nx mice, irrespective of age. Characteristically, NTT-MMP-2 protein expression was elevated in old control mice, in line with the qPCR results. NTT-MMP-2 expression was limited to the renal cortex, and to the tubulointerstitial area rather than the glomerular area. In terms of tissue damage, tubulointerstitial fibrosis was more severe in old 5/6Nx mice than in their young counterparts, whereas glomerulosclerosis was comparable in old and young 5/6Nx mice. The intracellular isoform of MMP-2 was induced by ageing, irrespective of the presence of diabetes or CKD, and its induction may be related to tubulointerstitial fibrosis in chronic kidney disease.