title: Mesenchymal stem cells suppress fibroblast proliferation and reduce skin fibrosis through a TGF-β3-dependent activation.
abstract: Recent studies showed that transplantation of mesenchymal stem cells (MSCs) significantly decreased tissue fibrosis; however, little attention has been paid to its efficacy on attenuating skin fibrosis, and the mechanism involved in its effect is poorly understood. In this work, we investigated the effects of MSCs on keloid fibroblasts and extracellular matrix deposition through paracrine actions and whether the antifibrotic properties of MSCs involved transforming growth factor-β (TGF-β)-dependent activation. In vitro experiments showed that conditioned media (CM) from MSCs decreased viability, a-smooth muscle actin expression, and collagen secretion of human keloid fibroblasts. In addition, TGF-β3 secreted by MSCs was expressed at high level under inflammatory environment, and blocking the activity of TGF-β3 apparently antagonized the suppressive activity of MSC CM, which demonstrated that TGF-β3 played a preponderant role in preventing collagen accumulation. In vivo studies showed that MSC CM infusion in a mouse dermal fibrosis model induced a significant decrease in skin fibrosis. Histological examination of tissue sections and immunohistochemical analysis for α-smooth muscle actin revealed that TGF-β3 of CM-mediated therapeutic effects could obviously attenuate matrix production and myofibroblast proliferation and differentiation. These findings suggest that TGF-β3 mediates the attenuating effect of MSCs on both the proliferation and extracellular matrix production of human keloid fibroblasts and decreases skin fibrosis of mouse model, thus providing new understanding and MSC-based therapeutic strategy for cutaneous scar treatment.
authors: Mudanjiang Medical College, Mudanjiang, People's Republic of China The First Affiliated Hospital, General Hospital of PLA, Beijing, People's Republic of China General Hospital of PLA, Beijing, People's Republic of China.
authors: Yan
authors: Y
authors: Wu
authors: The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors: Yan
authors: Y
authors: Peng
authors: Dongtai People's Hospital, Dongtai, People's Republic of China.
authors: Dongyun
authors: D
authors: Gao
authors: Peking University People's Hospital, Beijing, People's Republic of China.
authors: Changjiang
authors: C
authors: Feng
authors: Mudanjiang Medical College, Mudanjiang, People's Republic of China.
authors: Xiaohuan
authors: X
authors: Yuan
authors: Mudanjiang Medical College, Mudanjiang, People's Republic of China.
authors: Houzhong
authors: H
authors: Li
authors: Mudanjiang Medical College, Mudanjiang, People's Republic of China.
authors: Ying
authors: Y
authors: Wang
authors: Mudanjiang Medical College, Mudanjiang, People's Republic of China.
authors: Lan
authors: L
authors: Yang
authors: The First Affiliated Hospital, General Hospital of PLA, Beijing, People's Republic of China General Hospital of PLA, Beijing, People's Republic of China stellarahuang@sina.com wuyannini@126.com.
authors: Sha
authors: S
authors: Huang
authors: The First Affiliated Hospital, General Hospital of PLA, Beijing, People's Republic of China General Hospital of PLA, Beijing, People's Republic of China.
authors: Xiaobing
authors: X
authors: Fu
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012871:Skin Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D053782:Transforming Growth Factor beta3 / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
chemical_list: D053782:Transforming Growth Factor beta3; D012313:RNA
keywords: mesenchymal stem cells; paracrine; skin fibrosis; transforming growth factor-beta