Publications

Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.

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Journal of diabetes science and technology

Pilot Study of a Novel Application for Data Visualization in Type 1 Diabetes.

2017

Authors: Wong JC, Neinstein AB, Look H, Arbiter B, Chokr N, Ross C, Adi S

Science translational medicine

Could a coffee a day keep the inflammasome away?

2017

Authors: Bhattacharya M

Journal of clinical nursing

Group visits to encourage insulin initiation: targeting patient barriers.

2017

Authors: Kuo CR, Quan J, Kim S, Tang AH, Heuerman DP, Murphy EJ

Addiction (Abingdon, England)

Feasibility and safety of extended-release naltrexone treatment of opioid and alcohol use disorder in HIV clinics: a pilot/feasibility randomized trial.

2017

Authors: Korthuis PT, Lum PJ, Vergara-Rodriguez P, Ahamad K, Wood E, Kunkel LE, Oden NL, Lindblad R, Sorensen JL, Arenas V, Ha D, Mandler RN, McCarty D

Volume 12 of Issue 2 | PloS one

Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

2017

Authors: Kim SS, Shin N, Bae SS, Lee MY, Rhee H, Kim IY, Seong EY, Lee DW, Lee SB, Kwak IS, Lovett DH, Song SH

View Abstract

BACKGROUND

We 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.

METHODS

We 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.

RESULTS

Both 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).

CONCLUSIONS

The 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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