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

Tomer Avraham, Sanjay Daluvoy, Jaime Zampell, Alan Yan, Yosef S. Haviv, Stanley G. Rockson, Babak J. Mehrara

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


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.

Original languageEnglish
Pages (from-to)3202-3214
Number of pages13
JournalAmerican Journal of Pathology
Issue number6
StatePublished - 1 Jan 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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