Transforming growth factor-β and endoglin signaling orchestrate wound healing
- Department of Oncology, Microcirculation Research Group, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK
Physiological wound healing is a complex process requiring the temporal and spatial co-ordination of various signaling networks, biomechanical forces, and biochemical signaling pathways in both hypoxic and non-hypoxic conditions. Although a plethora of factors are required for successful physiological tissue repair, transforming growth factor beta (TGF-β) expression has been demonstrated throughout wound healing and shown to regulate many processes involved in tissue repair, including production of ECM, proteases, protease inhibitors, migration, chemotaxis, and proliferation of macrophages, fibroblasts of the granulation tissue, epithelial and capillary endothelial cells. TGF-β mediates these effects by stimulating signaling pathways through a receptor complex which contains Endoglin. Endoglin is expressed in a broad spectrum of proliferating and stem cells with elevated expression during hypoxia, and regulates important cellular functions such as proliferation and adhesion via Smad signaling. This review focuses on how the TGF-β family and Endoglin, regulate stem cell availability, and modulate cellular behavior within the wound microenvironment, includes current knowledge of the signaling pathways involved, and explores how this information may be applicable to inflammatory and/or angiogenic diseases such as fibrosis, rheumatoid arthritis and metastatic cancer.
Keywords: TGFβ, endoglin, wound healing, stem cells, progenitor cells, angiogenesis
Citation: Valluru M, Staton CA, Reed MWR and Brown NJ (2011) Transforming growth factor-β and endoglin signaling orchestrate wound healing. Front. Physio. 2:89. doi: 10.3389/fphys.2011.00089
Received: 07 September 2011;
Accepted: 10 November 2011;
Published online: 29 November 2011.
Edited by:Mariappan Muthuchamy, Texas A&M Health Science Center, USA
Reviewed by:Zhe Sun, University of MissouriColumbia, USA
Sanjukta Chakraborty, Texas A&M Health Science Center, USA
Gopal Jegadeesh Babu, University of Medicine and Dentistry of New Jersey, USA
Copyright: © 2011 Valluru, Staton, Reed and Brown. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Nicola J. Brown, Department of Oncology, Microcirculation Research Group, Faculty of Medicine, Dentistry and Health, University of Sheffield, Beech Hill Road, Sheffield, South Yorkshire 2RX, UK. e-mail: firstname.lastname@example.org