Open AccessSurfactant protein A induces the pathogenesis of renal fibrosis through binding to calreticulin
Author(s) -
Jian Hao,
Xin Zhao,
Weimin Yu,
Xianyu Huang,
Yirong Huang
Publication year - 2018
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2018.6919
Subject(s) - fibrosis , calreticulin , downregulation and upregulation , pathogenesis , apoptosis , western blot , biology , pulmonary fibrosis , cancer research , kidney , microbiology and biotechnology , medicine , chemistry , endocrinology , immunology , endoplasmic reticulum , biochemistry , gene
Renal fibrosis is a significant characteristic of chronic kidney diseases. Surfactant protein A (SP-A) is a recently identified fibrosis-associated factor in lung fibrosis; however, whether SP-A has the same role in renal fibrosis has remained elusive. The aim of the present study was to investigate the role of SP-A and its receptor calreticulin (CRT) in the pathogenesis of kidney fibrosis. The HK-2 human tubular epithelial cell line was cultured and treated with SP-A and SP-A + anti-CRT. The production of reactive oxygen species (ROS) at 30, 60 and 120 min was examined. Furthermore, cell apoptosis was assessed using an Annexin V assay and the expression of various proteins was measured using western blot analysis. In addition, the cell culture supernatants were collected and the expression of type I collagen was examined using ELISA. Compared with the control group, SP-A treatment significantly increased the ROS production, type I collagen secretion and cell apoptosis, which was partially inhibited by addition of anti-CRT. Furthermore, downregulation of matrix metalloproteinase (MMP)2 and -9 as well as upregulation of tissue inhibitor of metalloproteinase 1 indicated that SP-A treatment increased the degree of fibrosis in HK-2 cells, while addition of anti-CRT alleviated the fibrotic conditions. Finally, SP-A treatment significantly increased the expression of phosphorylated (p)-p38, p-p-65 and NADPH oxidase 2, which was partially inhibited by addition of anti-CRT. In conclusion, SP-A may participate in the pathogenesis of kidney fibrosis through binding to CRT and activate the mitogen-activated protein kinase/nuclear factor-κB-associated oxidative stress signaling pathway.