HOXD13调控SOX9基因可能参与先天足部软组织畸形的发生

doi:10.13418/j.issn.1001-165x.2020.06.013

Abstract

Abstract: Objective　To study the molecular mechanism of HOXD13 and SOX9 genes in the occurrence of foot soft tissue malformation of idiopathic congenital talipes equinovarus (ICTEV).　Methods 3 HOXD13 binding sites upstream of 5 'of SOX9 gene were predicted by the software, and luciferase activity of serial truncated and mutant vector in promoter region of SOX9 gene was detected. The binding effect of HOXD13 to the 3 sites of SOX9 gene promoter was verified by ChIP in vivo. The expression levels of HOXD13 and SOX9 were detected by qRT-PCR.　Results　A negative regulatory region between -1158 to -770 bp (site 1) and -512 to -368 bp (site 3) in the upstream of SOX9 gene 5' was found by the Luciferase. Between -770 and -512bp (locus 2) was a positive regulatory region. ChIP results showed that HOXD13 could bind to SOX9 locus 3.The mRNA expression of SOX9 gene was up-regulated by interference of HOXD13 expression.　Conclusions　The expression of SOX9 gene was up-regulated by HOXD13 in combination with the negative regulation region of SOX9 gene 5' upstream. The interference of HOXD13 up-regulated SOX9 gene expression may be related to the occurrence of soft tissue contracture on the ankle of foot.

Key words: Congenital foot deformity, 　HOXD13, 　SOX9, 　Development, 　Regulation

CLC Number:

Q291

WANG Zheng-dong, YAN Nan, LIU Li-ying, LI Shu, CHEN Yao, KONG Si-hui, LI Pei-yuan, JIN Chun-lian. Regulation of SOX9 by HOXD13 may be related to the occurrence of congenital foot malformation[J]. Chinese Journal of Clinical Anatomy, 2020, 38(6): 691-696.

References 14

[1]	Ponseti IV, Campos J. The classic: observations on pathogenesis and treatment of congenital clubfoot. 1972[J]. Clin Orthop Relat Res, 2009, 467(5): 1124-1132.
[2]	Wang ZD, Yan N, Liu LY, et al. SOX9 overexpression plays a potential role in idiopathic congenital talipes equinovarus[J]. Mol Med Rep, 2013, 7(3): 821-825.
[3]	王正东, 颜南, 王效杰, 等. Sox9基因在马蹄内翻足大鼠模型足踝软骨组织表达的实验研究 [J]. 沈阳医学院学报, 2012, 14(4): 199-201.
[4]	Zhang P, Jimenez SA, Stokes DG. Regulation of human COL9A1 gene expression. Activation of the proximal promoter region by SOX9[J]. J Biol Chem, 2003, 278(1): 117-123.
[5]	赵宁, 金春莲, 刘丽英, 等. COL1A1基因转录调控序列变异与单纯性马蹄内翻足的相关性 [J]. 遗传, 2008, 30(6): 723-727.
[6]	Ippolito E, De Maio F, Mancini F, et al. Leg muscle atrophy in idiopathic congenital clubfoot: is it primitive or acquired[J]? J Child Orthop, 2009, 3(3): 171-178.
[7]	Liu LY, Jin CL, Jiang L, et al. [Expression of COL9A1 gene and its polymorphism in children with idiopathic congenital talipes equinovarus][J]. Zhongguo Dang Dai Er Ke Za Zhi, 2011, 13(6): 478-481.
[8]	Wang LL, Fu WN, Li ZG, et al. Research of HOXD13 and FHL1 in idiopathic congenital talipes equinovarus[J]. Yi Chuan, 2008, 30(1): 46-50.
[9]	Zaib T, Ji W, Saleem K, et al. A heterozygous duplication variant of the HOXD13 gene caused synpolydactyly type 1 with variable expressivity in a Chinese family[J]. BMC Med Genet, 2019, 20(1): 203.
[10]	Wang LL, Jin CL, Liu LY, et al. [Analysis of association between 5' HOXD gene and idiopathic congenital talipes equinovarus][J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2005, 22(6): 653-656.
[11]	Ibrahim DM, Tayebi N, Knaus A, et al. A homozygous HOXD13 missense mutation causes a severe form of synpolydactyly with metacarpal to carpal transformation[J]. Am J Med Genet A, 2016, 170(3): 615-621.
[12]	Salsi V, Vigano MA, Cocchiarella F, et al. Hoxd13 binds in vivo and regulates the expression of genes acting in key pathways for early limb and skeletal patterning[J]. Dev Biol, 2008, 317(2): 497-507.
[13]	Wang LL, Fu WN, Li-Ling J, et al. HOXD13 may play a role in idiopathic congenital clubfoot by regulating the expression of FHL1[J]. Cytogenet Genome Res, 2008, 121(3-4): 189-195.
[14]	Cao DH, Jin CL, Ren MH, et al. The expression of Gli3, regulated by HOXD13, may play a role in idiopathic congenital talipes equinovarus[J]. BMC Musculoskelet Disord, 2009, 10: 142.

Regulation of SOX9 by HOXD13 may be related to the occurrence of congenital foot malformation

Knowledge

Abstract

Cite this article

share this article

References 14

Related Articles 7

Metrics

Comments

Recommended 0

[1]	Wang Menghui, GaoYan, Ye Xiaojian, Zhang Chunyang, Shao Guo, Wu Qirun. Analysis on the differential expression of mRNA in the dura mater of Ovis aries and the potential signaling pathways affecting cell migration [J]. Chinese Journal of Clinical Anatomy, 2023, 41(2): 187-193.
[2]	Li Fenjie, Chen Xi, Li Yangjie, Liao Jiaxin, Li Zhifu, Liu Anzhuo, Zhang Yueqiu, Yan Nan, Wang Zhengdong . Wnt/β-catenin signaling pathway involved in the deformity of congenital talipes equinovarus [J]. Chinese Journal of Clinical Anatomy, 2021, 39(5): 575-578.
[3]	LV Jing, DENG Li, GUAN Wei-kang, ZHU Yan, GUO Kan, GAO Xiao-qing, YANG Chao-xian. Expression changes of mitochondrial protein with age in mouse forebrain development [J]. Chinese Journal Of Clinical Anatomy, 2018, 36(4): 414-418.
[4]	ZHAO Hui, LIN Xiang-tao, XIAO Lian-xiang, WU Yong, DONG Jin-ye,ZHANG Zhong-he,TANG Yu-chun，LIU Shu-wei，WANG Guang-bing. MRI evaluation of fetal cervical spine length in normal second and third trimester of pregnancy [J]. Chinese Journal Of Clinical Anatomy, 2016, 34(2): 160-164.
[5]	MIAO Meng-Meng, LIN Xiang-Chao, LIU Shu-Wei, ZHANG Zhong-He, WANG Guang-Ban. The development of normal fetal lumbar spine: postmortem MRI study [J]. Chinese Journal Of Clinical Anatomy, 2012, 30(2): 185-188.
[6]	ZHANG 　Yi, YAN 　Yong, ZHANG Jian-Gang, HUANG 　Min, HE 　Xin. The expression of SDF-1α in the malformation of cortical development model rats [J]. Chinese Journal Of Clinical Anatomy, 2011, 29(1): 72-76.
[7]	ZHANG Min, SHU Xiao-Wen, WANG Xue-Er, ZHANG Lin. The experimental study of C57BL/6 mouse skin hair follicle development [J]. Chinese Journal Of Clinical Anatomy, 2010, 28(1): 74-.