The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease.
10.23876/j.krcp.2018.37.3.222
- Author:
Harin RHEE
1
;
Miyeun HAN
;
Sang Soo KIM
;
Il Young KIM
;
Hye Won LEE
;
Sun Sik BAE
;
Hong Koo HA
;
Eun Soon JUNG
;
Min Young LEE
;
Eun Young SEONG
;
Dong Won LEE
;
Soo Bong LEE
;
David H LOVETT
;
Sang Heon SONG
Author Information
1. Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. shsong0209@gmail.com
- Publication Type:Original Article
- Keywords:
Aging;
Chronic renal insufficiency;
Diabetes mellitus;
Matrix metalloproteinase-2
- MeSH:
Aging;
Animals;
Diabetes Mellitus*;
Diabetes Mellitus, Type 1;
Fibrosis;
Kidney;
Matrix Metalloproteinase 2*;
Mice*;
Mice, Inbred ICR;
Polymerase Chain Reaction;
Protein Isoforms*;
Renal Insufficiency, Chronic*;
Streptozocin
- From:Kidney Research and Clinical Practice
2018;37(3):222-229
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
