IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: Implications for diabetic nephropathy

Enrico Lupia, Sharon Elliot, Oliver Lenz, Feng Zheng, Masakazu Hattori, Gary E. Striker, Liliane J. Striker

Research output: Contribution to journalArticle

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Abstract

Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF- 1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 ± 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis.

Original languageEnglish
Pages (from-to)1638-1644
Number of pages7
JournalDiabetes
Volume48
Issue number8
DOIs
StatePublished - Aug 1 1999

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Mesangial Cells
Diabetic Nephropathies
Insulin-Like Growth Factor I
Collagen
Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinases
Inbred NOD Mouse
Extracellular Matrix
Tissue Inhibitor of Metalloproteinase-2
Messenger RNA
Matrix Metalloproteinase Inhibitors
Endocrinology
Metalloproteases
Neutralizing Antibodies

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

IGF-1 decreases collagen degradation in diabetic NOD mesangial cells : Implications for diabetic nephropathy. / Lupia, Enrico; Elliot, Sharon; Lenz, Oliver; Zheng, Feng; Hattori, Masakazu; Striker, Gary E.; Striker, Liliane J.

In: Diabetes, Vol. 48, No. 8, 01.08.1999, p. 1638-1644.

Research output: Contribution to journalArticle

Lupia, Enrico ; Elliot, Sharon ; Lenz, Oliver ; Zheng, Feng ; Hattori, Masakazu ; Striker, Gary E. ; Striker, Liliane J. / IGF-1 decreases collagen degradation in diabetic NOD mesangial cells : Implications for diabetic nephropathy. In: Diabetes. 1999 ; Vol. 48, No. 8. pp. 1638-1644.
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