Histamine inhibits differentiation of skin fibroblasts into myofibroblasts

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

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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 languageEnglish
Pages (from-to)434-439
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2015 Jun 14


  • Histamine
  • Myofibroblast
  • Skin fibroblast
  • Smad
  • TGF-β1
  • αSMA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Histamine inhibits differentiation of skin fibroblasts into myofibroblasts'. Together they form a unique fingerprint.

Cite this