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Thrombospondin-1 is the key activator of TGF-beta1 in human mesangial cells exposed to high glucose.
J Am Soc Nephrol. 2001 Apr; 12(4):703-12.JA

Abstract

Elevated levels of transforming growth factor-beta1 (TGF-beta1) are synthesized by human mesangial cells that are cultured in medium that contains high concentrations of glucose and mediate increased synthesis of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), and changes in the expression of other genes. TGF-beta1 is synthesized as a latent complex. Previous work indicated that high-glucose conditions also upregulate expression of thrombospondin-1 (TSP-1), a potential activator of latent TGF-beta1. With the use of the synthetic peptide GGWSHW, an inhibitor of the TSP-1 activation mechanism, endogenous TSP-1 is shown to be responsible for converting high levels of latent TGF-beta1 to bioactive growth factor over 3 wk of exposure of mesangial cells to 30 mM D-glucose. Peptide inhibition of TGF-beta1 activation by TSP-1 in high-glucose conditions completely suppressed increases in FN and PAI-1 expression. Treating mesangial cells maintained in high glucose with a TSP-1 antisense oligonucleotide reduced TSP-1 expression to levels found in 4 mM D-glucose cultures, prevented TGF-beta1 activation, and normalized expression of FN.

Authors+Show Affiliations

Molecular Pathology Section, Division of Biomedical Sciences, Imperial College School of Medicine, London, United Kingdom.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11274231

Citation

Yevdokimova, N, et al. "Thrombospondin-1 Is the Key Activator of TGF-beta1 in Human Mesangial Cells Exposed to High Glucose." Journal of the American Society of Nephrology : JASN, vol. 12, no. 4, 2001, pp. 703-12.
Yevdokimova N, Wahab NA, Mason RM. Thrombospondin-1 is the key activator of TGF-beta1 in human mesangial cells exposed to high glucose. J Am Soc Nephrol. 2001;12(4):703-12.
Yevdokimova, N., Wahab, N. A., & Mason, R. M. (2001). Thrombospondin-1 is the key activator of TGF-beta1 in human mesangial cells exposed to high glucose. Journal of the American Society of Nephrology : JASN, 12(4), 703-12.
Yevdokimova N, Wahab NA, Mason RM. Thrombospondin-1 Is the Key Activator of TGF-beta1 in Human Mesangial Cells Exposed to High Glucose. J Am Soc Nephrol. 2001;12(4):703-12. PubMed PMID: 11274231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombospondin-1 is the key activator of TGF-beta1 in human mesangial cells exposed to high glucose. AU - Yevdokimova,N, AU - Wahab,N A, AU - Mason,R M, PY - 2001/3/29/pubmed PY - 2001/7/20/medline PY - 2001/3/29/entrez SP - 703 EP - 12 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 12 IS - 4 N2 - Elevated levels of transforming growth factor-beta1 (TGF-beta1) are synthesized by human mesangial cells that are cultured in medium that contains high concentrations of glucose and mediate increased synthesis of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), and changes in the expression of other genes. TGF-beta1 is synthesized as a latent complex. Previous work indicated that high-glucose conditions also upregulate expression of thrombospondin-1 (TSP-1), a potential activator of latent TGF-beta1. With the use of the synthetic peptide GGWSHW, an inhibitor of the TSP-1 activation mechanism, endogenous TSP-1 is shown to be responsible for converting high levels of latent TGF-beta1 to bioactive growth factor over 3 wk of exposure of mesangial cells to 30 mM D-glucose. Peptide inhibition of TGF-beta1 activation by TSP-1 in high-glucose conditions completely suppressed increases in FN and PAI-1 expression. Treating mesangial cells maintained in high glucose with a TSP-1 antisense oligonucleotide reduced TSP-1 expression to levels found in 4 mM D-glucose cultures, prevented TGF-beta1 activation, and normalized expression of FN. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/11274231/Thrombospondin_1_is_the_key_activator_of_TGF_beta1_in_human_mesangial_cells_exposed_to_high_glucose_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=11274231 DB - PRIME DP - Unbound Medicine ER -