Impact of high-/middle-molecular-weight adiponectin on the synthesis and regulation of extracellular matrix in dermal fibroblasts

Hideki Nakasone, Kiriko Terasako-Saito, Rie Yamazaki, Miki Sato, Yukie Tanaka, Kana Sakamoto, Masakazu Kurita, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Tomohito Machishima, Masahiro Ashizawa, Shun ichi Kimura, Misato Kikuchi, Aki Tanihara, Junya Kanda, Shinichi Kako, Junji Nishida, Shigeki YamadaYoshinobu Kanda

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Adiponectin has been shown to play a critical role in immunity. Recently, we reported that the adiponectin levels after allogeneic stem cell transplantation were higher in recipients with chronic graft-versus-host disease (cGVHD). However, the effects of adiponectin on extracellular matrix (ECM) and regulatory factors in dermal fibroblasts remain unclear. We compared the messenger RNA (mRNA) levels of collagen type1 (COL1A), fibronectin 1 (FN1), matrix metalloproteinase (MMP)1, MMP3, tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, transforming growth factor-β (TGF-β), and TGF-β receptor 2 (TGF-βR2) in human normal dermal fibroblasts cultured with and without adiponectin, and we assessed the degree of synthesis of ECMs by immunofluorescent microscopy. Furthermore, we also assessed these mRNA levels after blocking of TGF-βR2. Adiponectin induced higher mRNA levels of FN1, MMP1, MMP3, TIMP1, TIMP3, and TGF-βR2 in a dose-dependent manner, but did not significantly affect COL1A or TGF-β. In addition, adiponectin was shown to upregulate FN1, MMPs, and TIMPs after blocking of TGF-βR2. Immunofluorescent microscopy revealed that adiponectin promoted a greater synthesis of ECMs than in the control invitro. The finding that adiponectin upregulated ECM-associated factors might mean that high levels of adiponectin could modulate dermal fibrosis was observed in recipients with cGVHD. Further basic investigation is warranted to elucidate whether the adiponectin-pathway could be a target for the treatment of sclerotic cGVHD.

Original languageEnglish
Pages (from-to)261-273
Number of pages13
JournalExperimental Hematology
Volume42
Issue number4
DOIs
Publication statusPublished - 2014 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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