Epigenetic regulation of the N-terminal truncated isoform of matrix metalloproteinase-2 (NTT-MMP-2) and Its presence in renal and cardiac diseases.
Nenhuma Miniatura disponível
Data
2021
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
Several clinical and experimental studies have documented a compelling and critical
role for the full-length matrix metalloproteinase-2 (FL-MMP-2) in ischemic renal injury,
progressive renal fibrosis, and diabetic nephropathy. A novel N-terminal truncated
isoform of MMP-2 (NTT-MMP-2) was recently discovered, which is induced by hypoxia
and oxidative stress by the activation of a latent promoter located in the first intron of the
MMP2 gene. This NTT-MMP-2 isoform is enzymatically active but remains intracellular
in or near the mitochondria. In this perspective article, we first present the findings about
the discovery of the NTT-MMP-2 isoform, and its functional and structural differences as
compared with the FL-MMP-2 isoform. Based on publicly available epigenomics data
from the Encyclopedia of DNA Elements (ENCODE) project, we provide insights into
the epigenetic regulation of the latent promoter located in the first intron of the MMP2
gene, which support the activation of the NTT-MMP-2 isoform. We then focus on its
functional assessment by covering the alterations found in the kidney of transgenic
mice expressing the NTT-MMP-2 isoform. Next, we highlight recent findings regarding
the presence of the NTT-MMP-2 isoform in renal dysfunction, in kidney and cardiac
diseases, including damage observed in aging, acute ischemia-reperfusion injury (IRI),
chronic kidney disease, diabetic nephropathy, and human renal transplants with delayed
graft function. Finally, we briefly discuss how our insights may guide further experimental
and clinical studies that are needed to elucidate the underlying mechanisms and the
role of the NTT-MMP-2 isoform in renal dysfunction, which may help to establish it as a
potential therapeutic target in kidney diseases.
Descrição
Palavras-chave
Mitochondria, Epigenomics, Acute kidney injury, Alternative promoter, Chronic kidney disease
Citação
CRUZ, J. de O. et al. Epigenetic regulation of the N-terminal truncated isoform of matrix metalloproteinase-2 (NTT-MMP-2) and Its presence in renal and cardiac diseases. Frontiers in genetics, v. 12, artigo 637148, fev. 2021. Disponível em: <https://www.frontiersin.org/articles/10.3389/fgene.2021.637148/full>. Acesso em: 11 out. 2022.