Lin L, Yamagata K, Nakayamada S, Sawamukai N, Yamaoka K, Sakata K, Nakano K, Tanaka Y, et al.
Biochemical and biophysical research communications. Date of publication 2015 Jul 31;volume 463(3):434-9.
1. Biochem Biophys Res Commun. 2015 Jul 31;463(3):434-9. doi:
10.1016/j.bbrc.2015.05.094. Epub 2015 May 31.
Histamine inhibits differentiation of skin fibroblasts into myofibroblasts.
Lin L(1), Yamagata K(2), Nakayamada S(2), Sawamukai N(2), Yamaoka K(3), Sakata
K(4), Nakano K(2), Tanaka Y(5).
Author information:
(1)The First Department of Internal Medicine, University of Occupational and
Environmental Health, Japan, Kitakyushu 807-8555, Japan; Department of
Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang
110022, China.
(2)The First Department of Internal Medicine, University of Occupational and
Environmental Health, Japan, Kitakyushu 807-8555, Japan.
(3)Division of Rheumatology, Keio University, Tokyo 160-8582, Japan.
(4)The First Department of Internal Medicine, University of Occupational and
Environmental Health, Japan, Kitakyushu 807-8555, Japan; Pharmacology Research
Laboratories I, Research Division, Mitsubishi Tanabe Pharma Corporation,
Yokohama, Kanagawa 227-0033, Japan.
(5)The First Department of Internal Medicine, University of Occupational and
Environmental Health, Japan, Kitakyushu 807-8555, Japan. Electronic address:
tanaka@med.uoeh-u.ac.jp.
Histamine and TGF-β, major mediators secreted by mast cells, are involved in skin
inflammation and play critical roles in the pathogenesis of systemic sclerosis.
However, the roles of signaling mechanisms in the development of skin fibrosis
remain largely unclear. Here we show that histamine suppressed the expression of
α smooth muscle actin (αSMA), a marker of myofibroblasts, induced by TGF-β1 in
skin fibroblasts. Histamine H1-receptor (H1R), but not H2-receptor (H2R) or
H4-receptor (H4R), was expressed on skin fibroblasts at both mRNA and protein
levels. Interestingly, an H1R antagonist, but not H2R or H4R antagonists,
antagonized the histamine-mediated suppression of αSMA expression by TGF-β1.
Correspondingly, phosphorylated Smad2 was detected after treatment with TGF-β1,
whereas the addition of histamine inhibited this phosphorylation. Taken together,
histamine-H1R decreased TGF-β1-mediated Smad2 phosphorylation and inhibited
differentiation of skin fibroblasts into myofibroblasts.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbrc.2015.05.094
PMID: 26036574 [Indexed for MEDLINE]
