Gliotoxin destructs the pulmonary epithelium barrier function by reducing cofilin oligomer formation to promote the dissolution of actin stress fibers. (October 2018)

• Record Type: Journal Article
• Authors: Zhang, Changjian; Liu, Xiaoyu; Chen, Fangyan; Hu, Yingsong; Li, Zhiqian; Liu, Yanxi; Han, Xuelin; Sun, Yansong; Han, Li
• Is Part Of: Microbial pathogenesis. Volume 123(2018)
• Page Start: 169
• Page End: 176
• Publication Date: 2018-10
• Subjects: Gliotoxin -- Cofilin oligomer -- Actin stress fibers -- A. fumigatus -- Pneumocyte epithelium; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2018.07.007
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: The destruction of pulmonary epithelium is a major feature of lung diseases caused by the fungal pathogen Aspergillus fumigatus (A. fumigatus) . Gliotoxin, a major mycotoxin of A. fumigatus, is widely postulated to be associated with the tissue invasion. However, the mechanism is unclear. In this study, we first discovered that cofilin, a regulator of actin dynamics in the pulmonary epithelial cells, existed mainly in the form of oligomer, which kept it unable to depolymerize actin filaments. Gliotoxin could reduce the formation of cofilin oligomer and promote the release of active cofilin monomer by regulating cofilin phosphorylation balance. Then, the active cofilin induced the dissolution of actin stress fibers to result in the disruption of pulmonary epithelium barrier function. Collectively, our study revealed a novel mechanism of gliotoxin destructing lung epithelium barrier function and for the first time indicated the role of cofilin oligomer in this process. Highlights: Gliotoxin destructs the pulmonary epithelium barrier. Cofilin oligomer exists in pulmonary epithelial cells. Gliotoxin reduces cofilin oligomer formation in epithelial cells. Gliotoxin induces cofilin phosphorylation in epithelial cells. The depolymerization of cofilin oligomer results in the dissolution of F-actin.