Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 13.05.2021

Dieser Artikel auf Deutsch


TGFbeta; TGF-ß; transforming growth factor-beta

This section has been translated automatically.

Transforming-Growth Factor-beta is a component and prototype of a large family of cytokines that can exert numerous biological processes in a variety of cell types. Thus, it is a cytokine that can exhibit different activities depending on the cell type, developmental stage, differentiation and cell cycle position of the target cell.

TGF-beta modulates proliferation, apoptosis, activation and differentiation of the corresponding target cells, among others.Among the most prominent activities are dermatological inhibition of epithelial cell proliferation, stimulation of extracellular matrix synthesis by fibroblasts, angiogenesis, protection of early thymic T cells from cell death, and regulation of mature T cells and macrophages. Due to its broad spectrum of activity, TGF-beta plays a central role in regeneration, immune response and tumorigenesis. Among other things, TGF-beta molecules influence the control of cell growth and differentiation in reparative processes as well as in the initiation of inflammation through chemotactic effects on inflammatory cells and fibroblasts.

General information
This section has been translated automatically.

  • TGF-beta exists in 3 isoforms:
    • TGF-beta 1
    • TGF-beta 2 and
    • TGF-beta 3.
  • Each isoform is encoded by a separate gene on different chromosomes. TGF-beta is present in most cells, but in a latent form and is activated when appropriate. In wound healing, binding to thrombospondin released by platelets appears to be essential for activation.
  • By action of TGF-beta as a ligand, two types of membrane receptors (type I and type II receptors) are initially activated. The TGF-beta type I receptor then phosphorylates Smad proteins which, after translocation into the nucleus, specifically regulate target genes. In healthy human skin, the type I and II receptors could be detected in the epidermis, skin appendages and vascular cells, but only in a few fibroblasts. In fibroblasts of keloids, increased expression of TGF-beta 1 and TGF-beta 2 was found compared to normal fibroblasts, with unchanged expression of TGF-beta 3. Especially TGF-beta 1 and 2 are considered to be fibrosis-inducing cytokines and are found in inflammatory skin in circumscritical scleroderma and progressive systemic scleroderma in humans.
  • During wound healing in humans, the number of dermal fibroblasts expressing TGF-beta receptor types I and II increases compared to normal skin and decreases again as healing progresses, but not in hypertrophic scarring.
  • Since TGF-beta is a wound healing-promoting cytokine, it is perplexing that Smad 3 knockout mice exhibit markedly accelerated wound healing after injury. The wound healing process is characterized by a release of TGF-beta from degranulating platelets that migrate into the wound area. TGF-beta causes a strong migration of monocytes and neutrophils into the region. These eliminate microorganisms and keep the wound edges clean, but also promote local inflammation through cytokine and protease release, which is not conducive to wound healing.
  • Fibroblasts also perform TGF-beta stimulated chemotaxis, proliferate strongly, cause wound margin contraction for better closure, and secrete matrix material such as collagen and fibronectin for tissue reconstruction. TGF-beta activates Smad-mediated transcription of the genes for collagen and fibronectin. The leukocytes and fibroblasts that have migrated into the wound area secrete TGF-beta again. Thus, its tissue level increases progressively and intensifies the migration until a compensatory downregulation of Smad 3 occurs. Only now does the activity of the described cells decrease. At the same time, TGF-beta levels decrease and the proliferation inhibition of keratinocytes is lifted. Thus, re-epithelialisation of the wound finally takes place.
  • The accelerated wound healing in the absence of TGF-beta or downregulation of Smad 3 is probably due to the increased keratinocyte proliferation. On the other hand, the reduced monocyte infiltration, which has no negative effect in the absence of wound contamination, prevents the development of inflammation. These two factors appear to more than compensate for the reduced matrix formation. The wounds of Smad-3-knock-outs heal within two days, whereas wild-type mice require an average of four to five days for this process. But evaluating this fact remains difficult. If matrix formation is underrepresented in Smad 3 deficiency, it may be at the expense of stable new tissue. Moreover, in the absence of immune cell immigration, defense mechanisms are inadequate in the presence of bacterial contamination.
  • Prospects for new drugs: The elucidation of the signaling cascades of TGF-beta as well as the knowledge of its physiological significance seem to be important for the development of new specific drugs. TGF agonists could be applicable in hyperproliferative skin diseases such as psoriasis, TGF antagonists in wound healing. Although TGF-beta is not yet available in any dosage form, its use as drug is definitely a possibility. The same applies for active agents which modify the TGF-beta metabolism or influence the TGF-beta signalling pathway. Here, substances are to be thought of which stimulate or inhibit receptors or those which modulate Smad proteins. The multitude of intervention possibilities at the different stages of the TGF-beta signalling cascade opens up promising perspectives in the search for new active substances.

This section has been translated automatically.

  1. Atamas SP et al (2003) The role of chemokines in the pathogenesis of scleroderma. Curr Opin Rheumatol 15: 772-777
  2. Denton CP et al (2001) Transforming growth factor-beta and connective tissue growth factor: key cytokines in scleroderma pathogenesis. Curr Opin Rheumatol 13: 505-511
  3. Massague J (1998) TGF-β signal transduction. Ann Rev Biochem 67: 753-791
  4. Itoh S et al (2000) Signaling of transforming growth factor-beta family members through Smad proteins. Eur J Biochem 267: 6954-6967
  5. Ozbilgin MK et al (2003) The roles of transforming growth factor type beta3 (TGF-beta3) and mast cells in the pathogenesis of scleroderma. Clin Rheumatol 22: 189-195
  6. Takagawa S et al (2003) Sustained activation of fibroblast transforming growth factor-beta/Smad signaling in a murine model of scleroderma. J Invest Dermatol 121: 41-50
  7. Yang X et al (1999) Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness toTGF-β. EMBO J 18: 1280-1291


Last updated on: 13.05.2021