mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis

• DOI: 10.1371/journal.pone.0138625
• Publication Date: 2015-09-18T18:59:29Z
• Authors: Yao-Song Gui; Lianmei Wang; Xinlun Tian; Xue Li; Aiping Ma; Weixun Zhou; Ni Zeng; Ji Zhang; Baiqiang Cai; Hongbing Zhang; Jing-Yu Chen; Kai-Feng Xu
• Keywords: TSC1; RPTOR; Sirolimus; Pathogenesis

The mammalian target of rapamycin (mTOR) signaling pathway in pulmonary fibrosis was investigated cell and animal models. mTOR overactivation alveolar epithelial cells (AECs) achieved the conditional inducible Tsc1 knock-down mice SPC-rtTA/TetO-Cre/Tsc1fx/+ (STT). Doxycycline caused consequently activation AECs for STT mice. Mice treated with bleomycin exhibited increased mortality compared control In wild-type C57BL/6J mice, pretreatment attenuated bleomycin-mediated fibrosis. Rapamycin-mediated mouse survival benefit inhibited by chloroquine, an autophagy inhibitor. Autophagosomes were decreased lungs after exposure. Rapamycin induced production autophagosomes diminished p62. We concluded that compromised are involved pathogenesis suppression enhancement may be used treatment