TY - JOUR
T1 - Histamine inhibits differentiation of skin fibroblasts into myofibroblasts
AU - Lin, Lin
AU - Yamagata, Kaoru
AU - Nakayamada, Shingo
AU - Sawamukai, Norifumi
AU - Yamaoka, Kunihiro
AU - Sakata, Kei
AU - Nakano, Kazuhisa
AU - Tanaka, Yoshiya
PY - 2015/6/14
Y1 - 2015/6/14
N2 - 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.
AB - 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.
KW - Histamine
KW - Myofibroblast
KW - Skin fibroblast
KW - Smad
KW - TGF-β1
KW - αSMA
UR - http://www.scopus.com/inward/record.url?scp=84930930487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930930487&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2015.05.094
DO - 10.1016/j.bbrc.2015.05.094
M3 - Article
C2 - 26036574
AN - SCOPUS:84930930487
VL - 463
SP - 434
EP - 439
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -