Surfactant protein A induces the pathogenesis of renal fibrosis through binding to calreticulin
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- Published online on: November 2, 2018 https://doi.org/10.3892/etm.2018.6919
- Pages: 459-464
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Abstract
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.
