TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells

Elizabeth Gore-Hyer, Daniel Shegogue, Malgorzata Markiewicz, Shianlen Lo, Debra Hazen-Martin, Eddie L. Greene, Gary Grotendorst, Maria Trojanowska

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-β and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-β and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, α2(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-β and CTGF in HMCs. However, only TGF-β stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-β and CTGF, although TGF-β was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.

Original languageEnglish (US)
Pages (from-to)F707-F716
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number4 52-4
DOIs
StatePublished - Oct 2002

Keywords

  • Collagen
  • Connective tissue growth factor
  • Epithelial-mesenchymal transdifferentiation
  • Mesangial cells
  • Tenascin
  • Transforming growth factor-β
  • Tubule epithelial cells

ASJC Scopus subject areas

  • Physiology
  • Urology

Fingerprint Dive into the research topics of 'TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells'. Together they form a unique fingerprint.

  • Cite this

    Gore-Hyer, E., Shegogue, D., Markiewicz, M., Lo, S., Hazen-Martin, D., Greene, E. L., Grotendorst, G., & Trojanowska, M. (2002). TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells. American Journal of Physiology - Renal Physiology, 283(4 52-4), F707-F716. https://doi.org/10.1152/ajprenal.00007.2002