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口腔天疱疮中凋亡的半胱天冬酶级联途径:一项免疫组织化学研究。

Caspase cascade pathways of apoptosis in oral pemphigus: An immunohistochemical study.

作者信息

Sanath Aparna K, Devy A Santha, Aithal Sanath, Kumar G Sathish, Prasad B Ganesh, Pradeep P S

机构信息

Departments of Oral Pathology and Microbiology, A. J. Institute of Dental Sciences, Mangalore, Karnataka, India.

Department of Oral Pathology and Microbiology, Indira Gandhi Institute of Dental Sciences, Puducherry, India.

出版信息

J Oral Maxillofac Pathol. 2018 Jan-Apr;22(1):48-53. doi: 10.4103/jomfp.JOMFP_79_17.

DOI:10.4103/jomfp.JOMFP_79_17
PMID:29731556
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5917541/
Abstract

BACKGROUND

Pemphigus is a group of autoimmune blistering diseases characterized by loss of keratinocyte cell adhesion that leads to blister formation clinically. Induction of apoptosis or of proapoptotic proteins by pemphigus immunoglobulin G (IgG) may be part of the mechanism by which IgG induces acantholysis. Some of the current data suggest that activation of proapoptotic proteins such as bax and caspase cysteine proteinases may sensitize cells to the acantholytic effects of pemphigus IgG. Thus, a central role of apoptosis in the mechanisms of blister induction is well recognized.

AIMS

This study aims (a) To find which pathway of apoptosis is involved in the pathogenesis of pemphigus and (b) to evaluate the expression of bax and caspase-8 and its key role in pemphigus.

MATERIALS AND METHODS

The study was conducted on 21 samples of oral pemphigus. The presence of apoptosis was evaluated in the sections taken from histopathologically diagnosed oral pemphigus archival blocks using peroxidase-antiperoxidase immunohistochemical method.

RESULTS

The expression and staining intensity of pro-apoptotic marker bax and apoptotic marker caspase-8 were observed in the various areas with varying intensity in different samples. The result was subjected to statistical analysis.

CONCLUSION

The results obtained in the present study suggest that the process of apoptosis occurs in PV. Hence, inhibition of apoptosis in the patients could reduce the severity of the lesions, and they could also represent new specific targets for pemphigus treatment.

摘要

背景

天疱疮是一组自身免疫性水疱性疾病,其特征是角质形成细胞间黏附丧失,临床上导致水疱形成。天疱疮免疫球蛋白G(IgG)诱导细胞凋亡或促凋亡蛋白可能是IgG诱导棘层松解的机制之一。目前的一些数据表明,促凋亡蛋白如bax和半胱天冬酶半胱氨酸蛋白酶的激活可能使细胞对天疱疮IgG的棘层松解作用敏感。因此,细胞凋亡在水疱形成机制中的核心作用已得到充分认识。

目的

本研究旨在(a)找出天疱疮发病机制中涉及的凋亡途径,以及(b)评估bax和半胱天冬酶-8的表达及其在天疱疮中的关键作用。

材料和方法

对21份口腔天疱疮样本进行研究。使用过氧化物酶-抗过氧化物酶免疫组化方法,在取自经组织病理学诊断的口腔天疱疮存档石蜡块的切片中评估细胞凋亡情况。

结果

在不同样本的不同区域观察到促凋亡标志物bax和凋亡标志物半胱天冬酶-8的表达及染色强度各不相同。对结果进行了统计分析。

结论

本研究获得的结果表明,寻常型天疱疮中存在细胞凋亡过程。因此,抑制患者的细胞凋亡可减轻病变严重程度,它们也可能代表天疱疮治疗的新的特异性靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/e54367b9c09e/JOMFP-22-48-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/466f492927fc/JOMFP-22-48-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/436e27b1255c/JOMFP-22-48-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/5f36e9e95ad8/JOMFP-22-48-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/ce7c006d6bcd/JOMFP-22-48-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/4a5980d0ad57/JOMFP-22-48-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/41786ac3d840/JOMFP-22-48-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/1f4151c7719c/JOMFP-22-48-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/50adc98cd917/JOMFP-22-48-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/ba56341ff334/JOMFP-22-48-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/e54367b9c09e/JOMFP-22-48-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/466f492927fc/JOMFP-22-48-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/436e27b1255c/JOMFP-22-48-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/5f36e9e95ad8/JOMFP-22-48-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/ce7c006d6bcd/JOMFP-22-48-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/4a5980d0ad57/JOMFP-22-48-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/41786ac3d840/JOMFP-22-48-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/1f4151c7719c/JOMFP-22-48-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/50adc98cd917/JOMFP-22-48-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/ba56341ff334/JOMFP-22-48-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111a/5917541/e54367b9c09e/JOMFP-22-48-g014.jpg

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本文引用的文献

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J Oral Pathol Med. 2013 May;42(5):409-14. doi: 10.1111/jop.12022. Epub 2012 Nov 27.
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Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris.FAK 的抑制作用可防止寻常型天疱疮新生儿小鼠模型中水疱的形成。
Exp Dermatol. 2012 Apr;21(4):254-9. doi: 10.1111/j.1600-0625.2012.01441.x. Epub 2012 Feb 10.
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Apoptotic pathways in the pathogenesis of pemphigus: targets for new therapies.
天疱疮发病机制中的凋亡途径:新疗法的靶点。
Curr Pharm Biotechnol. 2012 Aug;13(10):1877-81. doi: 10.2174/138920112802273236.
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Pemphigus autoimmunity: hypotheses and realities.天疱疮自身免疫:假说与现实。
Autoimmunity. 2012 Feb;45(1):7-35. doi: 10.3109/08916934.2011.606444. Epub 2011 Sep 23.
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The caspase pathway as a possible therapeutic target in experimental pemphigus.半胱天冬酶途径作为实验性天疱疮中一个可能的治疗靶点。
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Apoptotic pathways in pemphigus.天疱疮中的凋亡途径。
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Apoptosis in pemphigus.天疱疮中的细胞凋亡
Autoimmun Rev. 2009 Jun;8(7):533-7. doi: 10.1016/j.autrev.2009.01.011. Epub 2009 Feb 2.
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Apoptosis is not required for acantholysis in pemphigus vulgaris.寻常型天疱疮中的棘层松解不需要细胞凋亡。
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Pemphigus vulgaris autoantibodies induce apoptosis in HaCaT keratinocytes.寻常型天疱疮自身抗体可诱导HaCaT角质形成细胞凋亡。
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