Di S, Ziyou Y, Liu NF, et al.
Lymphatic research and biology. Date of publication 2016 Sep 1;volume 14(3):162-71.
1. Lymphat Res Biol. 2016 Sep;14(3):162-71. doi: 10.1089/lrb.2016.0010. Epub 2016
Sep 6.
Pathological Changes of Lymphedematous Skin: Increased Mast Cells, Related
Proteases, and Activated Transforming Growth Factor-β1.
Di S(1), Ziyou Y(1), Liu NF(1).
Author information:
(1)Department of Plastic and Reconstructive Surgery, Lymphology Centre, Shanghai
Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine ,
Shanghai, China .
BACKGROUND: Skin fibrosis is a clinically serious pathological process of
secondary lymphedema (SLE). Previous studies have shown that mast cells (MCs) are
involved in lymphedema (LE) and play a key role in the pathological process of
skin fibrosis. However, the role of the protease chymase and transforming growth
factor-β1 (TGF-β1) secreted by MCs in the fibrotic skins of patients with
secondary lower limb LE has not been explored.
METHODS AND RESULTS: In this study, full-thickness skin biopsies of
lymphedematous limbs from seven SLE patients and control samples from seven
healthy controls were harvested. The skin samples were assayed by Masson,
immunohistochemical, and immunofluorescence staining and were analyzed by western
blot and enzyme-linked immunosorbent assay. The number of MCs and the expression
of proteases, TGF-β1, and latency-associated peptide TGF-β1 (LAP TGF-β1) were
analyzed. The number of MCs and the expression of chymase, TGF-β1, and LAP TGF-β1
were increased in fibrotic skin compared with normal skin. The increased
expression of TGF-β1 on lymphatic vessels, endothelial cells, and in skin
interstitial tissues overlapped with chymase expression.
CONCLUSIONS: Our results demonstrate that chymase and TGF-β1 expression was
significantly increased in the fibrotic skin of secondary lower limb LE. The
increased expression of chymase in the skin may play an important role in the
development fibrosis in the lymphedematous skin. We speculate that chymase may
facilitate the release of LAP TGF-β1 to generate activated TGF-β1, and the
upregulation of active TGF-β1 can promote fibrosis in the SLE skin.
DOI: 10.1089/lrb.2016.0010
PMID: 27599355 [Indexed for MEDLINE]
