Bax-inhibiting peptide attenuates bleomycin-induced lung injury in mice.

Kunihiro Suzuki,Hironori Mikumo,Masako Arimura-Omori,Tetsuya Yokoyama,Saiko Ogata-Suetsugu,Taishi Harada,Naoki Hamada,Takashige Maeyama,Kazuyoshi Kuwano,Yoichi Nakanishi,Toyoshi Yanagihara,Eiji Harada

doi:10.1242/bio.026005

Kunihiro Suzuki, Hironori Mikumo + Show 10 more

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https://doi.org/10.1242/bio.026005

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Abstract

ABSTRACTBax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury. C57BL/6J mice were administered bleomycin and BIP-V5 intratracheally on day 0. Bronchoalveolar lavage fluid and lung tissue were obtained on day 7. Human pulmonary alveolar epithelial cells (A549 cells) and mouse pulmonary alveolar epithelial cells (LA-4 cells) were stimulated with bleomycin to induce apoptosis.Administration of BIP-V5 improved the survival rate and degree of bleomycin-induced lung injury by suppressing Bax activation in mice. BIP-V5 treatment decreased bleomycin-induced apoptosis of alveolar epithelial cell lines (A549 cells and LA-4 cells) by suppressing Bax activation. These results indicate that administration of BIP-V5 may constitute a novel therapeutic strategy against lung injury.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a fatal disease defined as a specific form of chronic fibrosing interstitial pneumonia and has the histological appearance of usual interstitial pneumonia
On day 7, the protein concentration and total number of cells in the bronchoalveolar lavage fluid (BALF) of mice treated with BLM and Bcl-2-associated X protein (Bax)-inhibiting peptide V5 (BIP-V5) were significantly lower than those in the BALF of the mice treated with BLM and negative control (NC) (Fig. 2A,B)
The transforming growth factor (TGF)-β1 levels in the BALF of mice treated with BLM were significantly increased

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a fatal disease defined as a specific form of chronic fibrosing interstitial pneumonia and has the histological appearance of usual interstitial pneumonia. The median survival of patients with IPF has been reported as 3–4 years from the onset of respiratory symptoms (American Thoracic Society and European Respiratory Society, 2002). The prognosis of this disease is relatively poor, the etiology of IPF remains unknown, and the efficacy of current therapeutic interventions is unsatisfactory (Behr, 2012; Richeldi et al, 2011). Alveolar epithelial cells are known as the primary site of lung damage in pulmonary fibrosis (Kuwano et al, 2004).

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