Abstract
It has long been recognized that fibrosis hinders lymphatic regeneration1,2 and thereby promotes the progression of lymphedema in the clinical settings in which this problem is known to occur. More recently, a series of newly acquired data suggest that this wound repair phenomenon is ascribable to the effects of transforming growth factor-β1 (TGF-β1).1–4 Capitalizing on the availability of EW-7197, a TGF-β1 receptor kinase inhibitor, in this issue of Lymphatic Research and Biology, Yoon and collaborators have investigated whether inhibition of the fibrotic process through this antagonist can ameliorate lymphedema in an experimental model of the disease.
The authors employed a modified murine tail model of acquired lymphedema 5 in this placebo-controlled short-term trial of EW-7197. In this model, the edematous response to lymphatic injury was statistically reduced within 2 to 4 weeks after institution of the therapeutic regimen. These findings were accompanied by indirect evidence of enhanced lymphangiogenesis, as can be inferred by the finding of an enhanced dermal vascular density as demonstrated by fluorescein isothiocyanate lymphography.
The findings of this study support the importance of fibrosis in the pathogenesis and maintenance of the lymphedematous state and suggest that further investigation of such therapeutic interventions might hold promise for the treatment of the human disease condition.