title: Impact of high-/middle-molecular-weight adiponectin on the synthesis and regulation of extracellular matrix in dermal fibroblasts.
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 in vitro. 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.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Kiriko
authors.initials: K
authors.lastname: Terasako-Saito
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamazaki
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Plastic Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kurita
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamasaki
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Machishima
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ashizawa
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Tanihara
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kako
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Nishida
authors.affiliation: Department of Pathology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. Electronic address: ycanda-tky@umin.ac.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D052242:Adiponectin / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D000090602:Collagen Type I, alpha 1 Chain; D020405:Dermis / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C067625:FN1 protein, human; D005353:Fibronectins; D018125:Receptors, Transforming Growth Factor beta; C560822:TIMP1 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1