GOLGA2 loss causes fibrosis with autophagy in the mouse lung and liver Sungjin Park a, 1 , Sanghwa Kim d, 1 , Min Jung Kim c, 1 , Youngeun Hong a , Ah Young Lee b , Hyunji Lee a , Quangdon Tran a , Minhee Kim a , Hyeonjeong Cho a , Jisoo Park a , Kwang Pyo Kim c, *** , Jongsun Park a, ** , Myung-Haing Cho b, e, f, g, h, * a Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea b Laboratoryof Toxicology, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea c Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Republic of Korea d Division of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Science, Seoul, Republic of Korea e Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, Republic of Korea f Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, Republic of Korea g Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea h Institute of GreenBio Science Technology, Seoul National University, Pyeongchang 25354, Republic of Korea article info Article history: Received 6 November 2017 Accepted 7 November 2017 Available online xxx Keywords: GOLGA2 knockout mice Golgi disruption Autophagy Lung fibrosis Liver fibrosis abstract Autophagy is a biological recycling process via the self-digestion of organelles, proteins, and lipids for energy-consuming differentiation and homeostasis. The Golgi serves as a donor of the double- membraned phagophore for autophagosome assembly. In addition, recent studies have demonstrated that pulmonary and hepatic fibrosis is accompanied by autophagy. However, the relationships among Golgi function, autophagy, and fibrosis are unclear. Here, we show that the deletion of GOLGA2, encoding a cis-Golgi protein, induces autophagy with Golgi disruption. The induction of autophagy leads to fibrosis along with the reduction of subcellular lipid storage (lipid droplets and lamellar bodies) by autophagy in the lung and liver. GOLGA2 knockout mice clearly demonstrated fibrosis features such as autophagy- activated cells, densely packed hepatocytes, increase of alveolar macrophages, and decrease of alveolar surfactant lipids (dipalmitoylphosphatidylcholine). Therefore, we confirmed the associations among Golgi function, fibrosis, and autophagy. Moreover, GOLGA2 knockout mice may be a potentially valuable animal model for studying autophagy-induced fibrosis. © 2017 Elsevier Inc. All rights reserved. 1. Introduction Autophagy is a degradation pathway for organelles, proteins, and lipids via lysosomal fusion, resulting in the recycling of these energy sources. Hepatic fibrosis is associated with autophagy. Usually, the damaged hepatocyte region is replaced though the replication of neighboring hepatocytes. However, under a condition of heavy damage, activated hepatic stellate cells (HSCs) transform into myofibroblast-like cells, which ultimately results in hepatic fibrosis. The activation of HSCs consumes an extreme amount of energy. To produce the required energy source, the autophagy process leads to degradation of the abundant lipid droplets (LDs) in the HSCs [1,2]. Several studies have shown that pulmonary fibrosis is also * Corresponding author. Laboratory of Toxicology, Research Institute for Veteri- nary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea. ** Corresponding author. Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea. *** Corresponding author. Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Republic of Korea. E-mail addresses: kimkp@khu.ac.kr (K.P. Kim), insulin@cnu.ac.kr (J. Park), mchotox@snu.ac.kr (M.-H. Cho). 1 These authors contributed equally to this work. Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc https://doi.org/10.1016/j.bbrc.2017.11.049 0006-291X/© 2017 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications xxx (2017) 1e7 Please cite this article in press as: S. Park, et al., GOLGA2 loss causes fibrosis with autophagy in the mouse lung and liver, Biochemical and Biophysical Research Communications (2017), https://doi.org/10.1016/j.bbrc.2017.11.049