CD14 Involvement in Third-degree Skin Burn-induced Myocardial Injury via the MAPK Signaling Pathway.
CD14 Involvement in Third-degree Skin Burn-induced Myocardial Injury via the MAPK Signaling Pathway.
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CD14 通过 MAPK 信号通路参与三度皮肤烧伤引起的心肌损伤。
DOI：
10.1007/s12013-021-00995-w
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发表时间：
2021
影响因子：
2.6
通讯作者：
Zhu Xiongxiang
中科院分区：
文献类型：
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作者：
Zhu Zhensen;Zou Ben;Gao Songying;Zhang Dongmei;Guo Jingdong;Chen Bo;Hou Haixin;Zhu Xiongxiang
本研究旨在探讨烧伤后心肌损伤的相关基因及相关通路。采用苏木精-伊红染色、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色和酶联免疫吸附试验检测大鼠Ⅲ度烧伤后心肌组织病理学结构、细胞凋亡和心肌损伤标志物。接下来，通过下一代测序（NGS）筛选差异表达的mRNA，然后通过定量逆转录-聚合酶链反应进行功能注释和关键基因验证。随后，筛选出CD 14，并将针对CD 14的小干扰RNA转染至H9 C2细胞，以进一步验证CD 14在烧伤损伤中的作用。结果表明，Ⅲ度烧伤可明显损害大鼠心肌组织结构，诱导心肌细胞凋亡，心肌损伤相关标志物水平升高，提示烧伤可引起大鼠心肌损伤。此外，NGS数据发现，三度烧伤可导致心肌组织中416个差异上调的mRNA和285个差异下调的mRNA。还公开了差异表达的mRNA主要富集在磷脂酰肌醇3-激酶/Akt、丝裂原活化蛋白激酶（MAPK）和肿瘤坏死因子信号通路中。此外，在用10%大鼠烧伤血清处理的H9 C2细胞中，细胞活力显著降低。CD 14的表达有显著差异，并筛选出用于进一步研究。与阴性对照组相比，烧伤血清可显著上调细胞外信号调节激酶、p38和c-Jun N-末端激酶的磷酸化水平，下调Bcl-2的表达，下调caspase-3的表达，而干扰CD 14的表达可逆转烧伤血清的作用。本研究表明烧伤血清处理可激活MAPK信号通路促进细胞凋亡，并可通过干扰CD 14的表达而逆转。
This study investigated the potential genes and related pathways in burn-induced myocardial injury. Rat myocardial injury induced by third-degree burn and the histopathological structures, apoptosis, and cardiac injury markers were then identified using hematoxylin & eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and enzyme-linked immunosorbent assay. Next, differentially expressed mRNAs were screened through next-generation sequencing (NGS), followed by functional annotation and key gene validation through quantitative reverse transcription-polymerase chain reaction. Subsequently, CD14 was screened out, and small interfering RNAs against CD14 were transfected to H9C2 cells to further verify the role of CD14 in burn-induced injury. The results showed that third-degree burn could markedly damage the structure of myocardial tissue, induce the apoptosis of myocardial cells, and increase the levels of myocardial injury-related markers, suggesting that burns could induce myocardial injury in rats. Besides, NGS data discovered that third-degree burn could result in 416 differentially upregulated mRNAs and 285 differentially downregulated mRNAs in myocardial tissue. It was also disclosed that differentially expressed mRNAs were mainly enriched in the phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase (MAPK), and tumor necrosis factor signaling pathways. Furthermore, cell viability was significantly decreased in H9C2 cells treated with 10% rat burn serum. CD14 was significantly differentially expressed and screened out for further studies. Treatment with burn serum can significantly upregulate the phosphorylation level of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase and the expression of cleaved caspase-3 and downregulate the expression of Bcl2 when compared with those in negative control of small interfering RNA transfected H9C2 cells, whereas interfering with CD14 expression reversed the effects of burn serum. The study demonstrated that burn serum treatment could activate the MAPK signaling pathway to promote cell apoptosis, and it can be reversed by interfering with the expression of CD14.