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

Li, Yushu; Wang, Xingzhi; Zhang, Lei; Yuan, Xueying; Hao, Jianbing; Ni, Jie; Hao, Lirong

doi:10.3892/ijmm.2018.3667

Cited by 7 publications

(12 citation statements)

References 72 publications

(85 reference statements)

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“…In our study, we found increased localization of α -SMA-positive cells in the SV. These results are in agreement with in vitro and in vivo studies that have shown areas of fibrosis-activated macrophages generating soluble mediators that modulate activation and proliferation of myofibroblasts [ 58 , 59 ]. Therefore, our findings suggest that cisplatin might promote the progression of SV fibrosis through the regulation of macrophage infiltration, secretion of IL-1 β , and accumulation of laminin and collagen IV.…”

Section: Discussionsupporting

confidence: 92%

Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis

Zhang

Cai

et al. 2020

Neural Plasticity

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The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cisplatin can damage SV and cause sensorineural hearing loss; however, the underlying mechanisms behind such injury are unclear. In this study, after the intraperitoneal injection of cisplatin (3 mg/kg/day for 7 days) in mice, we determined the auditory function by EP recording and auditory brainstem response (ABR) analysis, observed the ultrastructure of SV by transmission electron microscopy (TEM), and examined the expression and distribution of cell junction proteins by western blot, PCR, and immunofluorescence staining. We discovered that the EP was significantly reduced while ABR thresholds were significantly elevated in cisplatin-treated mice; cisplatin induced ultrastructural changes in marginal cells (MCs), endothelial cells (ECs), pericytes, etc. We found that cisplatin insulted auditory function not only by reducing the expression of zonula occludens protein-1 (ZO-1) in MCs of the SV but also by decreasing the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in MCs and basal cells (BCs). More importantly, cisplatin induced activations of perivascular-resident macrophage-like melanocytes (PVM/Ms) and interleukin-1beta (IL-1β) as well as increased expressions of profibrotic proteins such as laminin and collagen IV in SV. Thus, our results firstly showed that cisplatin induced fibrosis, inflammation, and the complex expression change of cell junctions in SV.

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Section: Discussionsupporting

confidence: 92%

Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis

Zhang

Cai

et al. 2020

Neural Plasticity

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“…Based on the results of a previous study (3), the RAW264.7 macrophage cell line was selected to examine the potential effect of AIF-1 on the aldosterone-induced activation of the PI3K/AKT/mTOR pathway; these cells constitutively express low levels of AIF-1 and facilitate the positive selection of stable transfectants for AIF-1 gene overexpression and knockdown. The results showed that aldosterone increased the mRNA expression levels of PI3K, AKT and mTOR compared with those in the untreated cells.…”

Section: Resultsmentioning

confidence: 99%

“…The sections were examined using light microscopy, and images of 10 non-repeating visual fields were randomly captured (magnification, ×400). Immunohistochemistry was performed as described previously (3). For blocking the antigen, 5% bovine serum albumin was used for 20 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…The preparation of protein samples from renal tissues and cells was performed as previously described (3). Briefly, protein was extracted in 1X SDS sample buffer following centrifugation at 12,000 × g for 15 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Allograft inflammatory factor 1 (AIF-1) serves an important role in aldosterone-induced renal fibrosis (3) and is secreted by macrophages, fibroblasts, endothelial cells and smooth muscle cells in a number of immune-inflammatory disorders (4,5). As a modulator of the immune response, AIF-1 promotes the proliferation and migration of macrophages and human vascular smooth muscle cells (6).…”

Section: Introductionmentioning

confidence: 99%

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Aldosterone promotes renal interstitial fibrosis via the AIF‑1/AKT/mTOR signaling pathway

Yuan

Wang

et al. 2019

Mol Med Report

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A number of studies have shown that aldosterone serves an important role in promoting renal interstitial fibrosis, although the specific mechanism remains to be elucidated. A previous study revealed that the fibrotic effect of aldosterone was associated with the expression of allograft inflammatory factor 1 (AIF-1) in RAW264.7 macrophage cells, in a time- and concentration-dependent manner. However, the exact mechanism through which aldosterone promotes renal interstitial fibrosis remains unknown. In the present study, the effects of aldosterone on renal inflammatory cell infiltration, collagen deposition and the expression levels of AIF-1, phosphatidylinositol 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mammalian target of rapamycin (mTOR), the oxidative stress factor NADPH oxidase 2 (NOX2) and nuclear transcription factor erythroid-related factor 2 (Nrf2) were assessed in normal rats, rats treated with aldosterone, rats treated with aldosterone and spironolactone and those treated with spironolactone only (used as the control). The effect of aldosterone on these factors was also investigated in the renal interstitium of unilateral ureteral obstruction (UUO) rats. Additionally, the AIF-1 gene was overexpressed and knocked down in macrophage RAW264.7 cells, and the effects of aldosterone on PI3K, AKT, mTOR, NOX2 and Nrf2 were subsequently investigated. The results showed that aldosterone promoted inflammatory cell infiltration, collagen deposition and the expression of AIF-1, PI3K, AKT, mTOR and NOX2, but inhibited the expression of Nrf2. In the UUO rats, aldosterone also promoted renal interstitial inflammatory cell infiltration, collagen deposition and the expression of AIF-1, NOX2, PI3K, AKT and mTOR, whereas the expression of Nrf2 was downregulated by aldosterone compared with that in the UUO-only group; the influence of aldosterone was counteracted by spironolactone in the normal and UUO rats. In vitro, aldosterone upregulated the expression levels of AKT, mTOR, NOX2 and Nrf2 in RAW264.7 cells compared with those in untreated cells. Suppressing the expression of AIF-1 inhibited the effects of aldosterone, whereas the overexpression of AIF-1 enhanced these effects in RAW264.7 cells. These findings indicated that aldosterone promoted renal interstitial fibrosis by upregulating the expression of AIF-1 and that the specific mechanism may involve AKT/mTOR and oxidative stress signaling.

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Is the proximal tubule the focus of tubulointerstitial fibrosis?

Peng

Wang

Zheng

et al. 2023

Heliyon

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

Cited by 7 publications

References 72 publications

Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis

Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis

Aldosterone promotes renal interstitial fibrosis via the AIF‑1/AKT/mTOR signaling pathway

Is the proximal tubule the focus of tubulointerstitial fibrosis?

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