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High glucose stimulates proliferation and collagen type I synthesis in renal cortical fibroblasts: mediation by autocrine activation of TGF-beta.
J Am Soc Nephrol. 1999 Sep; 10(9):1891-9.JA

Abstract

Renal tubular epithelial cells and interstitial fibroblasts are active participants in tubulointerstitial fibrosis, the best correlate of decreased glomerular filtration in diabetic nephropathy. It was reported previously that high ambient glucose stimulates transforming growth factor-beta (TGF-beta) mRNA and bioactivity, promotes cellular hypertrophy, and increases collagen synthesis in proximal tubular cells. This study evaluates the effects of high glucose and TGF-beta on the behavior of murine renal cortical fibroblasts (TFB) in culture. High glucose (450 mg/dl) significantly increased [3H]-thymidine incorporation (by 60 to 80% after 24 to 72 h) and cell number, without significantly increasing cell death when compared with normal glucose (100 mg/dl). There also was a transient increase in the mRNA of the c-myc and egr-1 early-response genes. Exogenous TGF-beta1 was promitogenic rather than antiproliferative in contrast to other renal cell types. Northern blot analysis demonstrated constitutive expression of TGF-beta1, -beta2, and -beta3 transcripts. Exposure to high glucose increased all three TGF-beta isoforms in a time-dependent manner. High glucose as well as exogenous TGF-beta1 also increased [3H]-proline incorporation, alpha2(I) collagen mRNA, and type I collagen protein (measured by immunoassay). Treatment with a neutralizing pan-selective monoclonal anti-TGF-beta antibody markedly attenuated the stimulation by high ambient glucose of thymidine incorporation, TGF-beta1 mRNA, and type I collagen mRNA and protein levels. It is concluded that high ambient glucose and exogenous TGF-beta1 share similar actions on renal fibroblasts. Moreover, the stimulation of cell proliferation and collagen type I synthesis in these cells by high ambient glucose are mediated by activation of an autocrine TGF-beta system.

Authors+Show Affiliations

Penn Center for Molecular Studies of Kidney Diseases, Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10477140

Citation

Han, D C., et al. "High Glucose Stimulates Proliferation and Collagen Type I Synthesis in Renal Cortical Fibroblasts: Mediation By Autocrine Activation of TGF-beta." Journal of the American Society of Nephrology : JASN, vol. 10, no. 9, 1999, pp. 1891-9.
Han DC, Isono M, Hoffman BB, et al. High glucose stimulates proliferation and collagen type I synthesis in renal cortical fibroblasts: mediation by autocrine activation of TGF-beta. J Am Soc Nephrol. 1999;10(9):1891-9.
Han, D. C., Isono, M., Hoffman, B. B., & Ziyadeh, F. N. (1999). High glucose stimulates proliferation and collagen type I synthesis in renal cortical fibroblasts: mediation by autocrine activation of TGF-beta. Journal of the American Society of Nephrology : JASN, 10(9), 1891-9.
Han DC, et al. High Glucose Stimulates Proliferation and Collagen Type I Synthesis in Renal Cortical Fibroblasts: Mediation By Autocrine Activation of TGF-beta. J Am Soc Nephrol. 1999;10(9):1891-9. PubMed PMID: 10477140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High glucose stimulates proliferation and collagen type I synthesis in renal cortical fibroblasts: mediation by autocrine activation of TGF-beta. AU - Han,D C, AU - Isono,M, AU - Hoffman,B B, AU - Ziyadeh,F N, PY - 1999/9/7/pubmed PY - 1999/9/7/medline PY - 1999/9/7/entrez SP - 1891 EP - 9 JF - Journal of the American Society of Nephrology : JASN JO - J Am Soc Nephrol VL - 10 IS - 9 N2 - Renal tubular epithelial cells and interstitial fibroblasts are active participants in tubulointerstitial fibrosis, the best correlate of decreased glomerular filtration in diabetic nephropathy. It was reported previously that high ambient glucose stimulates transforming growth factor-beta (TGF-beta) mRNA and bioactivity, promotes cellular hypertrophy, and increases collagen synthesis in proximal tubular cells. This study evaluates the effects of high glucose and TGF-beta on the behavior of murine renal cortical fibroblasts (TFB) in culture. High glucose (450 mg/dl) significantly increased [3H]-thymidine incorporation (by 60 to 80% after 24 to 72 h) and cell number, without significantly increasing cell death when compared with normal glucose (100 mg/dl). There also was a transient increase in the mRNA of the c-myc and egr-1 early-response genes. Exogenous TGF-beta1 was promitogenic rather than antiproliferative in contrast to other renal cell types. Northern blot analysis demonstrated constitutive expression of TGF-beta1, -beta2, and -beta3 transcripts. Exposure to high glucose increased all three TGF-beta isoforms in a time-dependent manner. High glucose as well as exogenous TGF-beta1 also increased [3H]-proline incorporation, alpha2(I) collagen mRNA, and type I collagen protein (measured by immunoassay). Treatment with a neutralizing pan-selective monoclonal anti-TGF-beta antibody markedly attenuated the stimulation by high ambient glucose of thymidine incorporation, TGF-beta1 mRNA, and type I collagen mRNA and protein levels. It is concluded that high ambient glucose and exogenous TGF-beta1 share similar actions on renal fibroblasts. Moreover, the stimulation of cell proliferation and collagen type I synthesis in these cells by high ambient glucose are mediated by activation of an autocrine TGF-beta system. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/10477140/High_glucose_stimulates_proliferation_and_collagen_type_I_synthesis_in_renal_cortical_fibroblasts:_mediation_by_autocrine_activation_of_TGF_beta_ L2 - https://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=10477140 DB - PRIME DP - Unbound Medicine ER -