The emerging role of transforming growth factor-β in kidney diseases

K. Sharma, F. N. Ziyadeh

Research output: Contribution to journalReview articlepeer-review

278 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) is a prototypical multifunctional cytokine, with growth being only one of its many functions. Its receptors and actions are germane to almost every cell in the body involved in tissue injury and repair, and its effects are best understood in the context of a cellular response to a changing environment. The broad areas in which TGF-β plays a crucial role include cell proliferation and extracellular matrix production. TGF-β is a key regulatory molecule in the control of the activity of fibroblasts and has been implicated in several disease states characterized by excessive fibrosis. In the kidney, TGF-β promotes tubuloepithelial cell hypertrophy and regulates the glomerular production of almost every known molecule of the extracellular matrix, including collagens, fibronectin, tenascin, and proteoglycans, as well as the integrins that are the receptors for these molecules. Furthermore, TGF-β blocks the destruction of newly synthesized extracellular matrix by upregulating the synthesis of protease inhibitors and downregulating the synthesis of matrix-degrading proteases such as stromelysin and collagenase. As will be discussed, there is a strong body of in vitro and in vivo evidence suggesting that persistent overproduction of TGF-β1 in glomeruli after the acute inflammatory stage of glomerulonephritis causes glomerulosclerosis. TGF-β may also be important in a variety of other chronic renal disorders characterized by hypertrophy and sclerosis, such as diabetic nephropathy. In this review we will attempt to offer a basic understanding of the cellular and molecular biology of TGF-β and its receptors, with special focus on the role of the TGF-β system in the kidney during development, growth, and disease.

Original languageEnglish (US)
Pages (from-to)F829-F842
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume266
Issue number6 35-6
StatePublished - Jan 1 1994
Externally publishedYes

Keywords

  • diabetes
  • fibrosis
  • glomerulonephritis
  • hypertrophy
  • matrix
  • mesangium
  • proliferation
  • prox imal tubule

ASJC Scopus subject areas

  • Physiology

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