Potential malignant transformation in the gastric mucosa of immunodeficient mice with persistent Mycoplasma penetrans infection.

Potential malignant transformation in the gastric mucosa of immunodeficient mice with persistent Mycoplasma penetrans infection.
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DOI:
10.1371/journal.pone.0180514
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Wang Y
Wang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao S;Shen D;Wang Y;Li L;Zhou L;Wang Y

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支原体感染已报告免疫功能低下的癌症患者;然而,目前尚不清楚持续的支原体感染是否会促进免疫功能低下的生物体中癌细胞的增殖。本研究的目的是在免疫缺陷的宿主模型中检测持续支原体感染和恶性转化之间的关系。用环磷酰胺建立免疫缺陷小鼠模型,用反式支原体(Mpe)感染小鼠胃粘膜细胞。18周后处死小鼠,通过荧光原位杂交(FISH)鉴定胃粘膜Mpe感染细胞。观察小鼠胃粘膜病理和超微结构变化,并采用Western blot检测多种原癌基因的表达。结果表明,免疫缺陷小鼠血液中检测到Mpe感染,FISH证实小鼠胃粘膜中存在Mpe持续感染。与对照组相比,感染组小鼠胃粘膜发生了病理和超微结构的恶性转化。与对照组相比,Mpe感染组小鼠p53和p21表达降低,H-ras表达升高。NF-κB p65亚单位在Mpe感染小鼠中表达增加,与TNF-α表达相似。Mpe感染组胃粘膜Bax表达低于对照组,Bcl-2表达高于对照组。总的来说,这些数据表明,持续性Mpe感染与免疫缺陷小鼠胃粘膜中多种原癌基因的异常表达相关,这些原癌基因可能促进恶性转化。
Mycoplasma infection has been reported in immunocompromised cancer patients; nevertheless, it is not clear if persistent Mycoplasma infection could facilitate the proliferation of cancer cells in immunocompromised organisms. The aim of this study was to examine the relationship between persistent Mycoplasma infection and malignant transformation in an immunodeficient host model. Immunodeficient mouse model was established using cyclophosphamide and mice gastric mucosal cells were infected with Mycoplasma penetrans (Mpe). After 18 weeks, mice were sacrificed and gastric mucosal Mpe infected cells were identified by fluorescence in situ hybridization (FISH). Moreover, pathological and ultrastructural changes in mice gastric mucosa were evaluated and the expression of multiple proto-oncogenes was examined by Western blot. Our data show that Mpe infection was detected in the blood of immunodeficient mice and Mpe persistent infection in mice gastric mucosa was confirmed by FISH. There were pathological and ultrastructural malignant transformation occurred in the gastric mucosa of infected mice compared to control mice. Mpe infected mice showed lower expression of p53 and p21 and higher H-ras expression compared to the control group. Moreover, expression of NF-κB p65 subunit increased in Mpe infected mice, similar to the TNF-α expression. Bax expression in gastric mucosa of Mpe infected mice was lower while Bcl-2 expression was higher than in the uninfected control group. Collectively these data demonstrate that persistent Mpe infection is associated with aberrant expression of multiple proto-oncogenes in gastric mucosa of immunodeficient mice which potentially facilitate the malignant transformation.
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