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Araya, J., Kojima, J., Takasaka, N., Ito, S., Fujii, S., Hara, H., Yanagisawa, H., Kobayashi, K., Tsurushige, C., Kawaishi, M., Kamiya, N., Hirano, J., Odaka, M., Morikawa, T., Nishimura, S.L., Kawabata, Y., Hano, H., Nakayama, K. and Kuwano, K. (2013) Insufficient Autophagy in Idiopathic Pulmonary Fibrosis. The American Journal of Physiology Lung Cellular and Molecular Physiology, 304, L56-L69.
https://doi.org/10.1152/ajplung.00213.2012

has been cited by the following article:

• TITLE: Constitutive AKT Activity Predisposes Lung Fibrosis by Regulating Macrophage, Myofibroblast and Fibrocyte Recruitment and Changes in Autophagy

  AUTHORS: Duaa Dakhlallah, Yijie Wang, Tierra A. Bobo, Emily Ellis, Xiaokui Mo, Melissa G. Piper, Timothy D. Eubank, Clay B. Marsh

  KEYWORDS: Pulmonary Fibrosis, AKT, CSF1, M-CSF Receptor, Macrophage, Myofibroblast, Fibrocytes, Autophagy

  JOURNAL NAME: Advances in Bioscience and Biotechnology, Vol.10 No.10, October 30, 2019

  ABSTRACT: The etiology and pathogenesis of pulmonary fibrosis is poorly understood. We and others reported that M-CSF/CSF-1, M-CSF-R and downstream AKT activation plays an important role in lung fibrosis in mice models and in IPF patients. To understand potential molecular pathways used by M-CSF-R activation to direct lung fibrosis, we used a novel transgenic mouse model that expresses a constitutively-active form of AKT, myristoylated AKT (Myr-Akt), driven by the c-fms (M-CSF-R) promoter. We were particularly interested in the basal immune state of the lungs of these Myr-Akt mice to assess M-CSF-R-related priming for lung fibrosis. In support of a priming effect, macrophages isolated from the lungs of unchallenged Myr-Akt mice displayed an M2-tropism, enhanced co-expression of M-CSF-R and α-SMA, reduced autophagy reflected by reduced expression of the key autophagy genes Beclin-1, MAP1-Lc3a(Lc3a), and MAP1-Lc3b(Lc3b), and increased p62/STSQM1 expression compared with littermate WT mice. Furthermore, Myr-Akt mice had more basal circulating fibrocytes than WT mice. Lastly, upon bleomycin challenge, Myr-Akt mice showed enhanced collagen deposition, increased F4/80+ and CD45+ cells, reduced autophagy genes Beclin-1, Lc3a, and Lc3b expression, and a shorter life-span than WT littermates. These data provide support that M-CSF-R/AKT activation may have a priming effect which can predispose lung tissue to pulmonary fibrosis.