TRB3 regulates pulmonary interstitial fibrosis through the MAPK signaling pathway

Wencheng Yu; Xiaoxia Song; Yaqiu Liu

TRB3 regulates pulmonary interstitial fibrosis through the MAPK signaling pathway

Int J Clin Exp Pathol. 2019 Sep 1;12(9):3247-3257. eCollection 2019.

Authors

Wencheng Yu¹, Xiaoxia Song², Yaqiu Liu³

Affiliations

¹ Department of Pneumology, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong Province, China.
² Department of Intensive Care Unit, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong Province, China.
³ Department of Pneumology, Zaozhuang Municipal Hospital Zaozhuang 277100, Shandong Province, China.

PMID: 31934168
PMCID: PMC6949843

Abstract

This study aims to investigate the effects of TRB3 on the EMT and MAPK signaling pathways in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. TRB3 adenovirus vector with green fluorescent protein (GFP) and TRB3-siRNA adenovirus vector were constructed for overexpression and down-regulation of TRB3, respectively. The pulmonary fibrosis mouse model was induced by bleomycin, and then treated with adenovirus on the next day. The mice were randomly killed at the 7^th (D7), 14^th (D14) and 28^th (D28) day, respectively. The lung tissues were collected for histopathologic observations, hydroxyproline determination, Immunohistochemistry, western blot and RT-qPCR to detect the expression of TRB3 and EMT-related proteins. Overexpression of TRB3 caused more severe pulmonary fibrosis (P<0.05), while downregulation of TRB3 significantly reduced pulmonary fibrosis (P<0.05). The expression of MAPK pathway-related and EMT-related genes and proteins was markedly upregulated by TRB3 overexpression (P<0.05), but prominently downregulated by TRB3-shRNA (P<0.05). In conclusion, exogenous regulation of TRB3 may have effects on bleomycin-induced pulmonary fibrosis in mice.

Keywords: EMT; MAPK signaling pathway; TRB3; idiopathic pulmonary fibrosis.