Transforming growth factor-β signal transduction and progressive renal disease

Jingfei Cheng, Joseph P. Grande

Research output: Contribution to journalShort survey

92 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) superfamily members are multifunctional growth factors that play pivotal roles in development and tissue homeostasis. Recent studies have underscored the importance of TGF-β in regulation of cell proliferation and extracellular matrix synthesis and deposition. TGF-β signaling is initiated by ligand binding to a membrane-associated receptor complex that has serine/threonine kinase activity. This receptor complex phosphorylates specific Smad proteins, which then transduce the ligand-activated signal to the nucleus. Smad complexes regulate target gene transcription either by directly binding DNA sequences, or by complexing with other transcription factors or co-activators. There is extensive crosstalk between the TGF-β signaling pathway and other signaling systems, including the mitogen-activated protein kinase pathways. The importance of TGF-β in regulation of cell growth has been emphasized by recent observations that mutations of critical elements of the TGF-β signaling system are associated with tumor progression in patients with many different types of epithelial neoplasms. TGF-β has emerged as a predominant mediator of extracellular matrix production and deposition in progressive renal disease and in other forms of chronic tissue injury. In this overview, recent advances in our understanding of TGF-β signaling, cell cycle regulation by TGF-β, and the role of TGF-β in progressive renal injury are highlighted.

Original languageEnglish (US)
Pages (from-to)943-956
Number of pages14
JournalExperimental Biology and Medicine
Volume227
Issue number11
StatePublished - Dec 1 2002

Keywords

  • Extracellular matrix
  • Kidney
  • Progressive renal disease
  • Signaling
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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