Histamine inhibits differentiation of skin fibroblasts into myofibroblasts

Lin Lin; Kaoru Yamagata; Shingo Nakayamada; Norifumi Sawamukai; Kunihiro Yamaoka; Kei Sakata; Kazuhisa Nakano; Yoshiya Tanaka

doi:10.1016/j.bbrc.2015.05.094

Histamine inhibits differentiation of skin fibroblasts into myofibroblasts

Lin Lin, Kaoru Yamagata, Shingo Nakayamada, Norifumi Sawamukai, Kunihiro Yamaoka, Kei Sakata, Kazuhisa Nakano, Yoshiya Tanaka

Department of Internal Medicine

Research output: Contribution to journal › Article

9 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	434-439
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	463
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2015.05.094
Publication status	Published - 2015 Jun 14

Keywords

Histamine
Myofibroblast
Skin fibroblast
Smad
TGF-β1
αSMA

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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Lin, L., Yamagata, K., Nakayamada, S., Sawamukai, N., Yamaoka, K., Sakata, K., Nakano, K., & Tanaka, Y. (2015). Histamine inhibits differentiation of skin fibroblasts into myofibroblasts. Biochemical and Biophysical Research Communications, 463(3), 434-439. https://doi.org/10.1016/j.bbrc.2015.05.094

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title = "Histamine inhibits differentiation of skin fibroblasts into myofibroblasts",

abstract = "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.",

keywords = "Histamine, Myofibroblast, Skin fibroblast, Smad, TGF-β1, αSMA",

author = "Lin Lin and Kaoru Yamagata and Shingo Nakayamada and Norifumi Sawamukai and Kunihiro Yamaoka and Kei Sakata and Kazuhisa Nakano and Yoshiya Tanaka",

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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

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