title: A novel truncated TGF-beta receptor II downregulates collagen synthesis and TGF-beta I secretion of keloid fibroblasts.
abstract: Hypertrophic scars and keloid are dermal proliferative disorders in wound healing. Transforming growth factor beta (TGF-beta) has been implicated in scar formation through the activation of fibroblasts and the acceleration of collagen deposition. Our study aimed to design a novel truncated (27-123 residues) type II TGF-beta receptor (tTGFbetaRII) and to determine its effects on the proliferation of keloid fibroblasts and the collagen synthesis as well as TGF-beta I expression of the cells. The coding sequences of TGF-beta I and tTGFbetaRII were amplified using RT-PCR and then cloned into pGBKT7 and pGADT7 vectors. A yeast two-hybrid experiment and a glutathione S-transferase (GST)-pull down assay were performed to verify the affinity of tTGFbetaRII to TGF-beta I. Our results indicated that treatment with tTGFbetaRII inhibited the growth of keloid fibroblasts and suppressed the synthesis of type I collagen in keloid fibroblasts in a concentration-dependent manner. Moreover, northern and western blot analysis revealed a decline of the TGF-beta I expression at both mRNA and protein levels after exposure to 5, 10 or 20 mug/ml of tTGFbetaRII. Together, our data suggested that the exogenous tTGFbetaRII can efficiently trap TGF-beta I from access to wild-type receptors and can suppress TGF-beta I triggered signals. Thus it may potentially be clinically applied to scar therapy.
authors.affiliation: College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.forename: Fen
authors.initials: F
authors.lastname: Guo
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhou
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Guo
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D007627:Keloid / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II