ArticlePloS one2017
Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 25 citations in OpenAlex.
- Biological Activity of Biomarkers Associated With Metastasis in Osteosarcoma Cell Lines.Cancer medicine · 2025Article
- Gel Zymography for the Evaluation of Matrix Metalloproteinase-2 and -9 in Aorta and Kidney Tissues.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The Possible Effect of β-Blocker Use on the Circulating MMP-2/TIMP-2 System in Patients with Chronic Kidney Disease on Conservative Treatment.Journal of clinical medicine · 2024Article
- Identification of biomarkers and prediction of upstream miRNAs in diabetic nephropathy.Frontiers in endocrinology · 2023Article
- Identification of tubulointerstitial genes and ceRNA networks involved in diabetic nephropathy via integrated bioinformatics approaches.Hereditas · 2022Article
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- Role of Akt1 in renal fibrosis and tubular dedifferentiation during the progression of acute kidney injury to chronic kidney disease.The Korean journal of internal medicine · 2021Article
- 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 · 2021Article
- Akt1 is involved in tubular apoptosis and inflammatory response during renal ischemia-reperfusion injury.Molecular biology reports · 2020Article
- Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3/NF-κB/MMP-2 axis.Cell death & disease · 2020Article
- Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Matrix Metalloproteinases in Diabetic Kidney Disease.Journal of clinical medicine · 2020Review
- TGF-β and Diabetic Nephropathy: Lessons Learned Over the Past 20 Years.The American journal of the medical sciences · 2020Article
- Deletion ofBioMed research international · 2020Article
- Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.PloS one · 2019Article
- The two isoforms of matrix metalloproteinase- 2 have distinct renal spatial and temporal distributions in murine models of types 1 and 2 diabetes mellitus.BMC nephrology · 2018Article
- The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease.Kidney research and clinical practice · 2018Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundWe recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.
methodsWe quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.
resultsBoth isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively).
conclusionsThe expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal disease.
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