title: The effects of WW2/WW3 domains of Smurf2 molecule on TGF-β signaling and arginase I gene expression.
abstract: Smad ubiquitination regulatory factor 2 (Smurf2) consists of multiple WW domains which can interact with Smad7 molecule and inhibit signaling of transforming growth factor-beta (TGF-β) cytokine. Arginase I (ArgI) is one of the main products of TGF-β signaling that plays important roles in tumor escape and airway tissue fibrosis and remodeling in asthma. In this study, the effects of TAT fused to WW2/WW3 (TAT-WW2/WW3) recombinant protein on TGF-β signaling and ArgI gene expression were evaluated on J774A.1 cell culture. For this purpose, interaction of TAT-WW2/WW3 with Smad7, mRNA expression of ArgI, and phosphorylated Smad3 (P-Smad3) were analyzed in TAT-WW2/WW3-treated J774A.1 cell. The results showed interaction of TAT-WW2/WW3 with Smad7, downregulation of ArgI gene expression (P < 0.05), and higher amount of P-Smad3 in the TAT-WW2/WW3-treated cells. In conclusion, we suggest that TAT-WW2/WW3 could interfere with TGF-β signaling and reduce ArgI gene expression. Since, ArgI has important effects on tissue remodeling in asthma and cancer progression, so these findings could be used to develop a new approach in the treatment of asthma and cancers.
authors.affiliation: Immunology Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Ganji
authors.affiliation: Immunology Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hani Mosayebzadeh
authors.initials: HM
authors.lastname: Roshan
authors.affiliation: Allergy Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Varasteh
authors.affiliation: Immunology Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Malihe
authors.initials: M
authors.lastname: Moghadam
authors.affiliation: Immunology Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Sankian
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic; D047468:Immunoprecipitation; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D051900:Smad3 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; C533325:Smurf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D001119:Arginase
keywords: Arginase I; J774A.1; P-Smad3; Smad7; Smurf2; TGF-β