奥马珠单抗调控Wnt/β-catenin信号通路对哮喘小鼠气道平滑肌细胞增殖和迁移的影响

doi:10.13481/j.1671-587X.20260518

Abstract

Abstract:

Objective To investigate the effect of omalizumab on the proliferation and migration of the airway smooth muscle cells （ASMCs） in the asthmatic mice by regulating wingless-type MMTV integration site family（Wnt）/β-catenin signal pathway. Methods Twelve mice were randomly divided into normal group and model group. The mouse model of asthma was constructed by sensitizing and stimulating the mixture of ovalbumin and aluminum hydroxide. The primary ASMCs were isolated from the bronchial tissue of the mice in normal group and model group. Immunofluorescence staining method was used to detect the positive expression of alpha-smooth muscle actin （α-SMA） in ASMCs. The ASMCs were divided into control group， asthma group， omalizumab group， iCRT3 （Wnt/β-catenin signaling pathway inhibitor） group， and omalizumab+SKL2001 （Wnt/β-catenin pathway activator） group. The ASMCs in control group were isolated from the bronchial tissues of mice in normal group. The ASMCs in other groups were isolated from the bronchial tissues of mice in model group and received corresponding treatments. 5-ethynyl-2'-deoxyuridine （EdU） staining method and cell counting kit-8 （CCK-8） method were used to detect the percentages of EdU-positive cells and proliferation activities in ASMCs in various groups. Wound healing assay was used to detect the wound healing rates in ASMCs in various groups. Enzyme-linked immunosorbent assay （ELISA） method was used to detect the levels of interleukin （IL）-6， IL-17， tumor necrosis factor-α （TNF-α）， IL-33， and IL-13 in the supernatants of ASMCs in various groups. Western blotting method was used to detect the expression levels of proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase 9 （MMP-9）， Wnt 3a， and β-catenin proteins in ASMCs in various groups. Results Over 98% of the cells isolated from the bronchial tissues of the mice in normal group and model group exhibited positive α-SMA expression， confirming the successful isolation of ASMCs. Compared with control group， the EdU-positive rate in ASMCs， proliferation activity， wound healing rate， the levels of IL-6， IL-17， TNF-α， IL-33， and IL-13 in the supernatant， and the expression levels of PCNA， MMP-9， Wnt 3a， and β-catenin proteins in ASMCs in asthma group were significantly increased （P<0.05）. Compared with asthma group， the EdU-positive rates in ASMCs， proliferation activities， wound healing rates， the levels of IL-6， IL-17， TNF-α， IL-33， and IL-13 in the supernatants， and the expression levels of PCNA， MMP-9， Wnt 3a， and β-catenin proteins in ASMCs in omalizumab group and iCRT3 group were significantly decreased （P<0.05）. Compared with omalizumab group， the above indices in ASMCs were significantly increased in omalizumab+SKL2001 group （P<0.05）. Conclusion Omalizumab inhibits the proliferation， migration and inflammatory response of ASMCs in the asthmatic mice， and its mechanism is related to inhibiting Wnt/β-catenin signal pathway.

Key words: Omalizumab, Asthma, Airway smooth muscle cells, Cell proliferation, Cell migration

CLC Number:

R562.25

Shuang REN,Xiaochao GAO,Yan WANG,Yanmei LIU,Wenxia MENG. Effects of omalizumab on proliferation and migration of airway smooth muscle cells in asthmatic mice by regulating Wnt/β-catenin signaling pathway[J].Journal of Jilin University(Medicine Edition), 2026, 52(5): 1369-1376.

Figures/Tables 7

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References 27

[1]	XIAO Y L， ZHU H， LEI J H， et al. miR-182/Sestrin2 affects the function of asthmatic airway smooth muscle cells by the AMPK/mTOR pathway［J］. J Transl Intern Med， 2023， 11（3）： 282-293.
[2]	LI W， LIU L Y， DUANQING M， et al. CLDN1 silencing suppresses the proliferation and migration of airway smooth muscle cells by modulating MMP14［J］. Autoimmunity， 2023， 56（1）： 2281223.
[3]	GU J Y， ZHOU D F. Long non-coding RNA MEG3 knockdown represses airway smooth muscle cells proliferation and migration via sponging miR-143-3p/FGF9 in asthma［J］. J Cardiothorac Surg， 2024， 19（1）： 314.
[4]	RAMOS-RAMÍREZ P， TLIBA O. Glucocorticoid insensitivity in asthma： the unique role for airway smooth muscle cells［J］. Int J Mol Sci， 2022， 23（16）： 8966.
[5]	MENZELLA F， JUST J， SAUERBECK I S， et al. Omalizumab for the treatment of patients with severe allergic asthma with immunoglobulin E levels above >1500 IU/mL［J］. World Allergy Organ J， 2023， 16（6）： 100787.
[6]	赵艳梅，闫萌，张振艳，等. 奥马珠单抗通过miR-217/E2F3轴介导SMAD3表达水平对大鼠支气管哮喘ASMCs增殖和迁移的影响及作用机制［J］. 中国老年学杂志， 2025， 45（1）： 199-205.
[7]	YUAN Y Y， ZHU H H， HUANG S H， et al. SFRP5 partially inhibits the proliferation and migration of airway smooth muscle cells in children with asthma by regulating the Wnt/β-catenin signaling pathway［J］. Discov Med， 2024， 36（181）： 323.
[8]	王盟，李慧，吕传峰. 钩藤碱固体脂质纳米粒抑制哮喘模型小鼠气道平滑肌细胞增殖的作用机制［J］. 中国药房， 2023， 34（9）： 1066-1070.
[9]	孟亮，王跃飞，陶亮，等. miR-1471通过调控Wnt/β-catenin通路对胶质瘤细胞EMT和侵袭的影响及其机制［J］.中国老年学杂志，2025，45（6）：1438-1441.
[10]	王晓英，韩志梅，李春艳. 藤黄酸抑制Wnt/β-catenin信号通路减轻牙周炎牙周膜细胞损伤及凋亡［J］. 激光生物学报， 2024， 33（6）： 567-576.
[11]	HU L L， LI L L， YAN C， et al. Baicalin inhibits airway smooth muscle cells proliferation through the RAS signaling pathway in murine asthmatic airway remodeling model［J］. Oxid Med Cell Longev， 2023， 2023： 4144138.
[12]	WANG J， WANG L， TIAN X F， et al. N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma［J］. PeerJ， 2023， 11： e14951.
[13]	YANG Q， MIAO Q， CHEN H， et al. Myocd regulates airway smooth muscle cell remodeling in response to chronic asthmatic injury［J］. J Pathol， 2023， 259（3）： 331-341.
[14]	BEAUFILS F， BERGER P. Commentary： Effect of curcumin nanoparticles on proliferation and migration of mouse airway smooth muscle cells and airway inflammatory infiltration［J］. Front Pharmacol， 2024， 15： 1432397.
[15]	LOVEL A G， MITCHELL D M. PCNA staining of retinal cryosections to assess microglial/macrophage proliferation［J］. Methods Mol Biol， 2023， 2636： 389-400.
[16]	KWON M R， PARK J S， KO E J， et al. Ibulocydine inhibits migration and invasion of TNBC cells via MMP-9 regulation［J］. Int J Mol Sci， 2024， 25（11）： 6123.
[17]	ZHOU T， CHEN X， FENG X. LncRNA DGCR5/miR-204-5p/SRSF7 axis regulates PDGF-BB-induced proliferation and migration of airway smooth muscle cells with potential role in asthma［J］. Autoimmunity， 2023， 56（1）： 2193678.
[18]	LANG D D， LIU Z M， LI D J. Safety and tolerability of omalizumab in children with allergic （IgE-mediated） asthma： a systematic review and meta-analysis［J］. Discov Med， 2023， 35（176）： 233-241.
[19]	杨文平，李刚，亓玉心，等. 奥马珠单抗对支气管哮喘大鼠肺功能及气道重塑的影响及机制研究［J］. 中国现代医学杂志， 2023， 33（14）： 16-21.
[20]	JIA X X， ZHU T T， HUANG Y， et al. Wnt/β-catenin signaling pathway regulates asthma airway remodeling by influencing the expression of c-Myc and cyclin D1 via the p38 MAPK-dependent pathway［J］. Exp Ther Med， 2019，18（5）：3431-3438.
[21]	LIU C Y， SHI S， GAO Y， et al. microRNA-485-3p promotes the inflammatory response and extracellular matrix deposition by activating Wnt/β-catenin signaling in human airway smooth muscle cells［J］. Crit Rev Eukaryot Gene Expr， 2023， 33（4）： 1-12.
[22]	LIU Y L， LI J N， CHEN R C， et al. Airway epithelial cells promote in vitro airway smooth muscle cell proliferation by activating the Wnt/β-catenin pathway［J］. Respir Physiol Neurobiol， 2025， 331： 104368.
[23]	WANG X H， ZHAO H Q， MA C H， et al. Gallic acid attenuates allergic airway inflammation via suppressed interleukin-33 and group 2 innate lymphoid cells in ovalbumin-induced asthma in mice［J］. Int Forum Allergy Rhinol， 2018， 8（11）： 1284-1290.
[24]	SHI Z H， XU M， CHEN X D， et al. The regulatory role of SFRP5/WNT5A axis in allergic rhinitis through inhibiting JNK pathway activation and lowering mucin generation in human nasal epithelial cells［J］. Exp Mol Pathol， 2021， 118： 104591.
[25]	REDHU N S， SALEH A， SHAN L Y， et al. Proinflammatory and Th2 cytokines regulate the high affinity IgE receptor （FcεRⅠ） and IgE-dependant activation of human airway smooth muscle cells［J］. PLoS One， 2009， 4（7）： e6153.
[26]	ABDULAAL W H， OMAR U M， ZEYADI M， et al. Pirfenidone ameliorates ANIT-induced cholestatic liver injury via modulation of FXR， NF-κB/TNF-α， and Wnt/GSK-3β/β-catenin signaling pathways［J］. Toxicol Appl Pharmacol， 2024， 490： 117038.
[27]	GÖKTUNA S I， SHOSTAK K， CHAU T L， et al. The prosurvival IKK-related kinase IKKϵ integrates LPS and IL17A signaling cascades to promote Wnt-dependent tumor development in the intestine［J］. Cancer Res， 2016， 76（9）： 2587-2599.

Group	Percentage ofEdU-positive cell(η/%)	Proliferation activity
Control	10.69±0.75	0.46±0.05
Asthma	28.74±1.92^*	1.27±0.16^*
Omalizumab	14.96±0.85^△	0.59±0.05^△
iCRT3	16.22±0.91^△	0.67±0.07^△
Omalizumab+SKL2001	20.89±1.73^#	0.89±0.08^#

Group	IL-6	IL-17	TNF-α	IL-33	IL-13
Control	131.67±7.22	26.69±1.58	54.62±3.25	15.69±1.04	43.68±2.59
Asthma	276.69±15.56^*	87.72±5.16^*	165.54±10.27^*	46.78±2.63^*	89.76±5.05^*
Omalizumab	162.28±10.43^△	39.83±2.25^△	78.86±4.46^△	26.81±1.54^△	56.81±2.96^△
iCRT3	150.67±8.89^△	46.69±2.58^△	83.61±5.29^△	28.67±1.83^△	61.62±4.04^△
Omalizumab+SKL2001	212.36±12.26^#	60.63±4.18^#	123.37±7.75^#	37.44±2.15^#	69.22±4.05^#

Group	PCNA	MMP-9	Wnt 3a	β-catenin
Control	1.06±0.19	0.71±0.09	0.54±0.06	0.15±0.02
Asthma	2.73±0.25^*	2.05±0.22^*	1.38±0.19^*	0.81±0.09^*
Omalizumab	1.56±0.14^△	1.08±0.15^△	0.69±0.07^△	0.29±0.03^△
iCRT3	1.71±0.16^△	1.19±0.18^△	0.80±0.09^△	0.35±0.04^△
Omalizumab+SKL2001	2.08±0.18^#	1.52±0.17^#	1.01±0.13^#	0.57±0.06^#

Effects of omalizumab on proliferation and migration of airway smooth muscle cells in asthmatic mice by regulating Wnt/β-catenin signaling pathway

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