MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction

Oncotarget
Kyung Mok KimHae Young Chung

Abstract

Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein-protein interaction (PPI). Both mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore, the interaction between MMP2 and A2M was verified by immunoprecipitation and immunohistochemistry. MMP2 activity was further measured under the presence or absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the absence of A2M-MMP2 interaction, was significantly decreased under the presence of interactions in aged kidney. We further hypothesized that the interaction between A2M-MMP2 played a role in the inactivation of MMP2 leading to accumulation of ECM including collagen type I and IV. Aged kidney showed highly accumulated MMP2 substrate proteins despite of increased MMP2 pr...Continue Reading

References

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Citations

Feb 13, 2020·Journal of Clinical Medicine·Nuria Garcia-FernandezMaría José Soler
Sep 5, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Emma J van BodegravenElly M Hol
Feb 13, 2021·International Journal of Molecular Sciences·María Julia BarisónBruno Dallagiovanna
Dec 24, 2021·Biochemical Society Transactions·Sandeep Satapathy, Mark R Wilson

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Methods Mentioned

BETA
RNA-Seq
immunoprecipitation
transgenic
PCR
electrophoresis

Software Mentioned

GrapdPad Prism
GraphPad

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