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Mutual regulation between miR-21 and the TGFß/Smad signaling pathway in human bronchial fibroblasts promotes airway remodeling.
Yu, Zhi-Wei; Xu, Ya-Qin; Zhang, Xiao-Juan; Pan, Jian-Rong; Xiang, Hong-Xia; Gu, Xiao-Hong; Ji, Shan-Bao; Qian, Jun.
Afiliação
  • Yu ZW; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Xu YQ; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Zhang XJ; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Pan JR; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Xiang HX; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Gu XH; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Ji SB; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
  • Qian J; a Department of Pediatrics , Wuxi Children's Hospital Affiliated to Nanjing Medical University , Wuxi , China.
J Asthma ; 56(4): 341-349, 2019 04.
Article em En | MEDLINE | ID: mdl-29621415
OBJECTIVE: Airway remodeling is an important pathological feature of asthma. Excessive deposition of extracellular matrix (e.g., collagen) secreted from fibroblasts is a major factor contributing to airway remodeling. Currently, the mechanism by which collagen continues to be oversynthesized in the airway remains unclear. In this study, we investigated the role of the microRNA-21 (miR-21) and TGFß/Smad signaling pathway in human bronchial fibroblasts (HBFs), and explored the regulatory mechanism of airway remodeling. METHODS: HBFs were cultured in vitro and treated with the transforming growth factor ß (TGFß), receptor inhibitor (SB431542), and TGFß1. miR-21 and Smad7 overexpressing lentiviruses, as well as an miR-21 interfering lentivirus were constructed and transfected into HBFs. Western blotting was used to determine the expression of airway remodeling-related proteins and proteins in the TGFß/Smad signaling pathway. miR-21 expression was measured by quantitative real-time PCR. RESULTS: The high expression of miR-21 induced by TGFß1 was reduced following the treatment with the SB431542 in HBFs. Smad7 overexpression inhibited the elevated expression of the COL I protein induced by miR-21 overexpression in HBFs. Inhibiting miR-21 expression upregulated the level of Smad7 protein, thus reducing the expression of airway remodeling-related proteins induced by TGFß1 stimulation in HBFs. CONCLUSIONS: TGFß1 can induce miR-21 expression in HBFs through the TGFß/Smad signaling pathway to promote airway remodeling. miR-21 downregulates Smad7, activates the TGFß/Smad signaling pathway, and promotes airway remodeling. Mutual regulation between miR-21 and the TGFß/Smad signaling pathway in HBFs promotes airway remodeling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Fator de Crescimento Transformador beta / MicroRNAs / Proteína Smad7 / Remodelação das Vias Aéreas Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: J Asthma Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Fator de Crescimento Transformador beta / MicroRNAs / Proteína Smad7 / Remodelação das Vias Aéreas Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: J Asthma Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China