Wang Ningqing, Zhang Jiangchao, Lv Haixiang, Liu Zhenjiang
Department of Orthopedics, Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
Front Pediatr. 2022 Jul 22;10:890109. doi: 10.3389/fped.2022.890109. eCollection 2022.
Congenital talipes equinovarus (CTEV) is one of the most common congenital limb defects in children, which is a multifactorial and complex disease that associates with many unknown genetic, social-demographic, and environmental risk factors. Emerging evidence proved that gene expression or mutation might play an important role in the occurrence and development of CTEV. However, the underlying reasons and involved mechanisms are still not clear. Herein, to probe the potential genes and related signaling pathways involved in CTEV, we first identified the differentially expressed genes (DEGs) by mRNA sequencing in pediatric patients with CTEV compared with normal children. The gene of was upregulated, and was downregulated at the transcriptional level. Western blot and quantitative polymerase chain reaction (qRT-PCR) results also showed that the expression of in CTEV was enhanced, and the was decreased. Furthermore, the Knock-in (+) and Knock-out (-) transgenic mice were used to verify the effects of these two genes in the CTEV, and the results of which showed that both and were closely related to the CTEV. We also investigated the effect of the PI3K-AKT3 signaling pathway in CTEV by measuring the relative expression of several key genes using Western blot and qRT-PCR. In line with the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis data, the PI3K-AKT3 signaling pathway might play a potentially important role in the regulation of pathological changes of CTEV. This study will provide new ideas for the mechanism investigation and prenatal diagnosis of CTEV.
先天性马蹄内翻足（CTEV）是儿童中最常见的先天性肢体缺陷之一，是一种多因素的复杂疾病，与许多未知的遗传、社会人口统计学和环境风险因素相关。新出现的证据表明，基因表达或突变可能在CTEV的发生和发展中起重要作用。然而，其潜在原因和涉及的机制仍不清楚。在此，为了探究参与CTEV的潜在基因和相关信号通路，我们首先通过mRNA测序确定了CTEV患儿与正常儿童相比的差异表达基因（DEG）。在转录水平上，[基因名称1]基因上调，[基因名称2]基因下调。蛋白质免疫印迹法（Western blot）和定量聚合酶链反应（qRT-PCR）结果也表明，CTEV中[基因名称1]的表达增强，而[基因名称2]降低。此外，使用[基因名称1]敲入（+）和[基因名称2]敲除（-）转基因小鼠来验证这两个基因在CTEV中的作用，结果表明[基因名称1]和[基因名称2]均与CTEV密切相关。我们还通过蛋白质免疫印迹法和qRT-PCR测量几个关键基因的相对表达，研究了PI3K-AKT3信号通路在CTEV中的作用。与京都基因与基因组百科全书（KEGG）分析数据一致，PI3K-AKT3信号通路可能在CTEV病理变化的调节中发挥潜在重要作用。本研究将为CTEV的机制研究和产前诊断提供新思路。
