Blockade of transforming growth factor-β1 accelerates lymphatic regeneration during wound repair Journal Article

Authors: Avraham, T.; Daluvoy, S.; Zampell, J.; Yan, A.; Haviv, Y. S.; Rockson, S. G.; Mehrara, B. J.
Article Title: Blockade of transforming growth factor-β1 accelerates lymphatic regeneration during wound repair
Abstract: Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study,we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-β1 in the regulation of this response. We determined TGF-β expression patterns in matched biopsy specimens collected from lymphedematous and normal limbs of patients with secondary lymphedema. To determine the role of TGF-β in regulating tissue fibrosis, we used a mouse model of lymphedema and inhibited TGF-β function either systemically with a monoclonal antibody or locally by using a soluble, defective TGF-β receptor. Lymphedematous tissue demonstrated a nearly threefold increase in the number of cells that stained for TGF-β1. TGF-β inhibition markedly decreased tissue fibrosis, increased lymphangiogenesis, and improved lymphatic function compared with controls. In addition, inhibition of TGF-β not only decreased TGF-β expression in lymphedematous tissues, but also diminished inflammation, migration of T-helper type 2 (Th2) cells , and expression of profibrotic Th2 cytokines. Similarly, systemic depletion of T-cells markedly decreased TGF-β expression in tail tissues. Inhibition of TGF-β function promoted lymphatic regeneration, decreased tissue fibrosis , decreased chronic inflammation and Th2 cell migration, and improved lymphatic function. The use of these strategies may represent a novel means of preventing lymphedema after lymph node resection. Copyright © American Society for Investigative Pathology.
Keywords: clinical article; controlled study; human tissue; protein expression; nonhuman; mouse; animal tissue; interleukin 13; interleukin 4; animal experiment; animal model; monoclonal antibody; lymphangiogenesis; lymphedema; soft tissue; wound healing; fibrosis; th2 cell; genetic transfection; transforming growth factor beta1; cytokine production; antiinflammatory activity; adenovirus vector; cd4 antigen; cd3+ t lymphocyte; lymphatic drainage; chronic inflammation; transforming growth factor beta antibody; transforming growth factor beta receptor 2; lymphocyte migration
Journal Title: American Journal of Pathology
Volume: 177
Issue: 6
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2010-12-01
Start Page: 3202
End Page: 3214
Language: English
DOI: 10.2353/ajpath.2010.100594
PROVIDER: scopus
PMCID: PMC2993295
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: AJPAA" - "Source: Scopus"
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MSK Authors
  1. Sanjay Daluvoy
    17 Daluvoy
  2. Babak Mehrara
    257 Mehrara
  3. Tomer Avraham
    33 Avraham
  4. Jamie Christine Zampell
    29 Zampell
  5. Alan Yan
    20 Yan