Open Access

Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype

  • Authors:
    • Yushu Li
    • Xingzhi Wang
    • Lei Zhang
    • Xueying Yuan
    • Jianbing Hao
    • Jie Ni
    • Lirong Hao
  • View Affiliations

  • Published online on: May 10, 2018     https://doi.org/10.3892/ijmm.2018.3667
  • Pages: 861-872
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophages have been identified as a key cell type in the pathogenesis of renal interstitial fibrosis (RIF). However, the mechanism through which macrophages drive fibrosis remains unclear. The current study focuses on the effects and possible underlying mechanism of allograft inflammatory factor‑1 (AIF‑1), an inflammation‑responsive scaffold protein expressed and secreted by macrophages, in promoting fibroblasts to a profibrotic phenotype. In vivo experiments indicated that AIF‑1, CD68 and α‑smooth muscle actin (α‑SMA) were upregulated in kidney tissues of mice subjected to unilateral ureteric obstruction, while their expressions were inhibited by an aldosterone receptor antagonist, spironolactone. Double immunofluorescence staining revealed that AIF‑1 expression co‑localized with CD68‑positive macrophages in the renal interstitium, indicating that AIF‑1 expression in macrophages was increased in the RIF animal model. Furthermore, to identify the role of AIF‑1 in promoting fibrosis, its expression and secretion by the RAW264.7 macrophage cell line were detected in vitro. The expression levels of α‑SMA, phosphorylated p38 (p‑p38) and fibronectin (FN) in fibroblasts were examined subsequent to co‑culture with macrophages. The increase in AIF‑1 expression and secretion was confirmed in RAW264.7 cells in response to aldosterone. After 72 h of co‑culture between fibroblasts and macrophages stimulated with aldosterone, the α‑SMA expression was induced in fibroblasts, with significantly increased expression levels of FN and p‑p38 observed. In addition, AIF‑1 expression was reduced by stable transfection of RAW264.7 cells with AIF‑1 small interfering RNA, resulting in significantly reduced expression levels of α‑SMA, p‑p38 and FN in fibroblasts co‑cultured with macrophages as compared with normal macrophages. These findings indicate that the expression of AIF‑1 in macrophages is critical for the activation of renal fibroblasts to a profibrotic phenotype. AIF‑1 expression was upregulated in macrophages, and may be a novel mechanism linking macrophages to the promotion of RIF via the p38 signaling pathway.
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August-2018
Volume 42 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li Y, Wang X, Zhang L, Yuan X, Hao J, Ni J and Hao L: Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype. Int J Mol Med 42: 861-872, 2018
APA
Li, Y., Wang, X., Zhang, L., Yuan, X., Hao, J., Ni, J., & Hao, L. (2018). Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype. International Journal of Molecular Medicine, 42, 861-872. https://doi.org/10.3892/ijmm.2018.3667
MLA
Li, Y., Wang, X., Zhang, L., Yuan, X., Hao, J., Ni, J., Hao, L."Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype". International Journal of Molecular Medicine 42.2 (2018): 861-872.
Chicago
Li, Y., Wang, X., Zhang, L., Yuan, X., Hao, J., Ni, J., Hao, L."Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype". International Journal of Molecular Medicine 42, no. 2 (2018): 861-872. https://doi.org/10.3892/ijmm.2018.3667