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致病性、非致病性和机会性皮肤细菌对细胞周期和分化标志物的调控。

Regulation of cell cycle and differentiation markers by pathogenic, non-pathogenic and opportunistic skin bacteria.

作者信息

Younis Sidra, Deeba Farah, Fatima Saeed Rida, Mothana Ramzi A, Ullah Riaz, Faheem Muhammad, Javed Qamar, Blumenberg Miroslav

机构信息

Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan.

Department of Biochemistry, Quaid-e-Azam University, Islamabad, Pakistan.

出版信息

Saudi J Biol Sci. 2022 Mar;29(3):1717-1729. doi: 10.1016/j.sjbs.2021.10.058. Epub 2021 Nov 2.

Abstract

Skin is the first line of defense against the physical, chemical and the biological environment. It is an ideal organ for studying molecular responses to biological infections through a variety of skin cells that specialize in immune responses. Comparative analysis of skin response to pathogenic, non-pathogenic, and commensal bacteria would help in the identification of disease specific pathways for drug targets. In this study, we investigated human breast reduction skin responses to , , and TLR1/2 agonist using Affymetrix microarray chips. The Pam3CSK4 solution and bacterial cultures were prepared and inoculated in steel rings, that were placed on the acetone treated epidermis in a petri dish. After 24 h incubation, 8 mm punch biopsies were taken from the center of the ring, and RNA was extracted. The genome-wide expression was then analyzed using Affymetrix HG-133A gene chip microarray. We found that the and boosted the production of extracellular matrix components and attenuated the expression of differentiation markers. The above responses were mediated through the TLR2 pathway. Skin also responded to and by inducing the genes of the cell cycle machinery; this response was not TLR2-dependent. induced, whereas suppressed the genes associated with apoptosis; this was also not TLR2-dependent. Moreover, apparently did not lead to changes in gene expression. We conclude that the breast reduction skin is a very useful model to study the global gene expression in response to bacterial treatments.

摘要

皮肤是抵御物理、化学和生物环境的第一道防线。它是一个理想的器官,可通过多种专门参与免疫反应的皮肤细胞来研究对生物感染的分子反应。对皮肤对致病性、非致病性和共生细菌的反应进行比较分析,将有助于确定针对药物靶点的疾病特异性途径。在本研究中,我们使用Affymetrix微阵列芯片研究了人类缩乳皮肤对 、 、 和TLR1/2激动剂的反应。制备了Pam3CSK4溶液和细菌培养物,并接种在钢环中,将钢环放置在培养皿中经丙酮处理的表皮上。孵育24小时后,从环的中心取8毫米的打孔活检组织,提取RNA。然后使用Affymetrix HG-133A基因芯片微阵列分析全基因组表达。我们发现 和 促进了细胞外基质成分的产生,并减弱了分化标志物的表达。上述反应是通过TLR2途径介导的。皮肤对 和 也有反应,诱导细胞周期机制的基因;这种反应不依赖TLR2。 诱导,而 抑制与凋亡相关的基因;这也不依赖TLR2。此外, 显然没有导致基因表达的变化。我们得出结论,缩乳皮肤是研究细菌处理后全球基因表达的非常有用的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4674/8913412/d9096ad2c309/ga1.jpg

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