Kidney Res Clin Pract.  2018 Sep;37(3):222-229. 10.23876/j.krcp.2018.37.3.222.

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

Affiliations
  • 1Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. shsong0209@gmail.com
  • 2Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.
  • 3Research Institute for Convergence of Biomedical Science and Technology and Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
  • 4Medical Research Center for Ischemic Tissue Regeneration, Medical Research Institute, Pusan National University, Yangsan, Korea.
  • 5Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Korea.
  • 6Department of Urology, Pusan National University Hospital, Busan, Korea.
  • 7Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California, San Francisco School of Medicine, San Francisco, CA, USA.

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.

Keyword

Aging; Chronic renal insufficiency; Diabetes mellitus; Matrix metalloproteinase-2

MeSH Terms

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
Matrix Metalloproteinase 2
Protein Isoforms
Streptozocin
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