In vitro and in vivo study of the expression of the Syk/Ras/c‑Fos pathway in chronic glomerulonephritis

Gao,Jiarong; Wei,Liangbing; Song,Junmei; Jiang,Hui; Gao,Yachen; Wu,Xi; Xu,Shuangzhi

doi:10.3892/mmr.2018.9355

In vitro and in vivo study of the expression of the Syk/Ras/c‑Fos pathway in chronic glomerulonephritis

Authors:
- Jiarong Gao
- Liangbing Wei
- Junmei Song
- Hui Jiang
- Yachen Gao
- Xi Wu
- Shuangzhi Xu
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Affiliations: Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, P.R. China, College of Chemistry and Material Engineering, Chaohu University, Hefei, Anhui 230031, P.R. China , Department of Urology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, P.R. China
Published online on: August 3, 2018 https://doi.org/10.3892/mmr.2018.9355
Pages: 3683-3690
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic glomerulonephritis (CGN) is the most common form of glomerular disease; however, its associated molecular mechanisms remain unclear. Spleen tyrosine kinase (Syk) is a key mediator of B‑receptor signaling on the surface of inﬂammatory cells. The primary target for R406 is Syk. The aim of the present study was to investigate the molecular mechanisms involved in a rat model of CGN induced by adriamycin (ADR) and in the rat glomerular mesangial cell line, HBZY‑1, stimulated by lipopolysaccharide (LPS). CGN was induced in the rat models by two intravenous injections of ADR into the tail: 3.5 mg/kg ADR was given on the first day and 3.0 mg/kg on the fourteenth day. HBZY‑1 cells were incubated with 0.5 µg/ml LPS for 48 h. The pathological alterations in the kidney tissues were observed by hematoxylin and eosin staining. The 24 h urinary protein, blood urea nitrogen (BUN) and creatinine levels were measured using an automatic biochemistry analyzer. The mRNA expression levels of Syk, Ras, mitogen activated protein kinase kinase (MEK), extracellular signal regulated kinase (ERK)1/2 and c‑Fos was measured by reverse transcription‑quantitative polymerase chain reaction. Subsequently, the protein levels of phosphorylated (p)‑Syk, Ras, p‑MEK1/2, p‑ERK1/2 and c‑Fos were measured by western blot analysis. In the model group, 24 h urinary protein, BUN and creatinine levels were increased when compared with the normal group (P<0.05). In addition, compared with the normal group, the mRNA and protein levels of the Syk/Ras/c‑Fos pathway components in vitro and in vivo were markedly increased, inhibiting the abnormal cell viability of mesangial cells. In conclusion, the results of the present study suggested a potential role for the Syk/Ras/c‑Fos signaling pathway in CGN, which indicated the necessity for further investigation at the clinical level.

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