HIF-VEGF-Notch signaling pathway may be involved in the occurrence of equinovarus deformity

doi:10.13418/j.issn.1001-165x.2022.1.12

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Chinese Journal of Clinical Anatomy ›› 2022, Vol. 40 ›› Issue (1) : 62-66. DOI: 10.13418/j.issn.1001-165x.2022.1.12

HIF-VEGF-Notch signaling pathway may be involved in the occurrence of equinovarus deformity

Zhang Zhenyi1, Chen Xi2，Wang Qian3*

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Abstract

Objective　To study the molecular mechanism of equinovarus deformity.　Methods　HE staining was used to observe the difference of foot and ankle tissue structure in model group and control group. The expressions of hypoxia inducible factor 1 (HIF-1), vascular endothelial growth factor (VEGF) and Notch-1 in the tissues of foot and ankle of rats in model group and control group were detected by immunohistochemical staining, Western Blot and qRT-PCR.　Results　Microscopic observation results showed that compared with the control group, the tissue structure of the foot and ankle in the experimental group was relatively disordered, with enlarged tissue space, loose soft tissue and aggregation contracture of local soft tissue. Immunohistochemical staining, Western Blot and qRT-PCR results showed that compared with the control group, the expression of HIF-1 down-regulated in ankle tissue of the experimental group, and the expression of VEGF and Notch-1 decreased.　Conclusions 　HIF-VEGF-Notch signaling pathway may be related to the occurrence of varus foot deformity.

Key words

Hypoxia inducible factor 1 (HIF1) / 　Vascular endothelial growth factor (VEGF) / 　Notch signaling pathway / 　Congenital talipes equinovarus

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Zhang Zhenyi, Chen Xi, Wang Qian. HIF-VEGF-Notch signaling pathway may be involved in the occurrence of equinovarus deformity[J]. Chinese Journal of Clinical Anatomy. 2022, 40(1): 62-66 https://doi.org/10.13418/j.issn.1001-165x.2022.1.12

References

[1] Gelfer Y, Wientroub S, Hughes K, et al. Congenital talipes equinovarus: a systematic review of relapse as a primary outcome of the Ponseti method[J]. Bone Joint J, 2019, 101-B (6): 639-645. DOI: 10.1302/0301-620X.101B6.BJJ-2018-1421.R1.
[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. DOI: 10.3892/mmr.2012.1245.
[3] 王正东, 颜南, 刘丽英, 等. HOXD13调控SOX9基因可能参与先天足部软组织畸形的发生[J].中国临床解剖学杂志, 2020, 38(6): 691-696. DOI: 10.13418/j.issn.1001-165x.2020.06.013.
[4] Chu HX, Jones NM. Changes in Hypoxia-Iinducible Factor-1 (HIF-1) and regulatory prolyl hydroxylase (PHD) enzymes following hypoxic-ischemic injury in the neonatal rat[J]. Neurochem Res, 2016, 41(3): 515-522. DOI: 10.1007/s11064-015-1641-y.
[5] Mi DH, Fang HJ, Zheng GH, et al. DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high-glucose conditions, potentially through the SIRT1/HIF-1/VEGF pathway[J]. CNS Neurosci Ther, 2019, 25(3): 323-332. DOI: 10.1111/cns.13042.
[6] Zheng LL, Huang J, Su Y, et al. Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI-2 and HIF-1alpha/VEGF in a l-NAME induced rat model[J]. Drug Dev Res, 2019, 80(8): 1120-1127. DOI: 10.1002/ddr.21596.
[7] Zhang B, Zhao Q, Li YS, et al. Moxibustion alleviates intervertebral disc degeneration via activation of the HIF-1alpha/VEGF pathway in a rat model[J]. Am J Transl Res, 2019, 11(9): 6221-6231. PMID: 31632589.
[8] Li LH, Yin XJ, Ma N, et al. Desferrioxamine regulates HIF-1 alpha expression in neonatal rat brain after hypoxia-ischemia[J]. Am J Transl Res, 2014, 6(4): 377-383. PMID: 25075254.
[9] Xiang YX, Du PC, Zhang XM, et al. Acetylpuerarin inhibits oxygen-glucose deprivation-induced neuroinflammation of rat primary astrocytes via the suppression of HIF-1 signaling[J]. Exp Ther Med, 2018, 16(3): 2689-2695. DOI: 10.3892/etm.2018.6509.
[10]Li YC, Hichson JA, Ambrosi DJ, et al. ABT-165, a dual variable domain immunoglobulin (DVD-Ig) targeting DLL4 and VEGF, demonstrates Ssuperior efficacy and favorable safety profiles in preclinical models[J]. Mol Cancer Ther, 2018, 17(5): 1039-1050. DOI: 10.1158/1535-7163.MCT-17-0800.
[11]Lobov I, Mikhailova N. The role of Dll4/Notch signaling in normal and pathological ocular angiogenesis: Dll4 controls blood vessel sprouting and vessel remodeling in normal and pathological conditions[J]. J Ophthalmol, 2018, 2018: 3565292. DOI: 10.1155/2018/3565292.
[12]Wen ZK, Shen Y, Berry G, et al. The microvascular niche instructs T cells in large vessel vasculitis via the VEGF-Jagged1-Notch pathway[J]. Sci Transl Med, 2017, 9(399): eaal3322. DOI: 10.1126/scitranslmed.aal3322.
[13]Lee D, Kim D, Choi YB, et al. Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits tumor progression and angiogenesis[J]. MAbs, 2016, 8(5): 892-904. DOI: 10.1080/19420862.2016.1171432.
[14]Polansky H, Schwab H. How a disruption of the competition between HIF-1 and p53 for limiting p300/CBP by latent viruses can cause disease[J]. Genes Cancer, 2018, 9(5-6): 153-154. DOI: 10.18632/genesandcancer.178.