The effect of incretin hormone GLP-1 on the phenotypic profile of mononuclear cells in fetal growth restriction
- 作者: Krasny A.M.1, Kan N.E.1, Borisova A.G.1, Soldatova E.E.1, Tyutyunnik V.L.1, Volochaeva M.V.1
-
隶属关系:
- Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
- 期: 编号 10 (2024)
- 页面: 74-81
- 栏目: Original Articles
- URL: https://ogarev-online.ru/0300-9092/article/view/270938
- DOI: https://doi.org/10.18565/aig.2024.156
- ID: 270938
如何引用文章
开放存取
##reader.subscriptionAccessGranted##
订阅存取
详细
Relevance: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates insulin secretion, and elevated GLP-1 level is in fetal growth restriction. GLP-1 can bind to its membrane receptors on leukocytes and change their phenotype.
Objective: To study the impact of GLP-1 on the phenotypic profile of peripheral blood mononuclear cells in pregnant women with fetal growth restriction and identify potential diagnostic markers.
Materials and methods: The study was conducted in two stages. In stage one, the impact of the GLP-1 receptor agonist liraglutide on the phenotypic profile of peripheral blood mononuclear cells in 12 pregnant women (6 patients with fetal growth restriction and 6 patients with normal pregnancy) was assessed using flow cytometry. In stage two, 56 pregnant women were enrolled in the study, and divided into two groups. The main group consisted of 32 women with fetal growth restriction. The comparison group consisted of 24 patients with normal pregnancy.
The diagnostic significance of the obtained markers (CD4, CD8, CD86 and CD163) was evaluated by measuring their counts and expression levels in the peripheral blood of pregnant women.
Results: In vitro assessment of the effect of liraglutide on mononuclear cells in the peripheral blood of pregnant women showed statistically significant decrease in CD8+ lymphocyte number (p=0.03), reduction in CD8 expression in lymphocytes (p=0.03) and elevated expression of CD163 on monocytes (p=0.05). In the blood of pregnant women with fetal growth restriction, statistically significant relatively high levels of CD4+ (p=0.02) and CD163+ (p=0.001) monocytes and relatively low levels of CD8+ lymphocytes (p=0.006) were found. At the same time, the levels of CD163 expression in the main group were significantly elevated (p=0.02), while the levels of CD86 expression on monocytes was reduced (p=0.02). The ROC analysis showed the potential diagnostic value of the relative level of CD163+ monocytes in the blood of pregnant women for the diagnosis of fetal growth restriction (AUC=0.83).
Conclusion: The obtained data showed that in fetal growth retardation glucagon-like peptide-1 triggers a specific cellular response, which is manifested by activation of a pronounced anti-inflammatory effect in women’s blood. Studying this signaling pathway may help to understand new mechanisms of fetal growth restriction and identify potential markers that will enable to verify this pregnancy complication at the antenatal stage.
作者简介
Alexey Krasny
Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
编辑信件的主要联系方式.
Email: alexred@list.ru
ORCID iD: 0000-0001-7883-2702
PhD, Head of the Cytology Laboratory
俄罗斯联邦, MoscowNatalia Kan
Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: kan-med@mail.ru
ORCID iD: 0000-0001-5087-5946
SPIN 代码: 5378-8437
Scopus 作者 ID: 57008835600
Researcher ID: B-2370-2015
Dr. Med. Sci., Professor, Deputy Director of Science
俄罗斯联邦, MoscowAnastasia Borisova
Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: vvv92@list.ru
PhD Student
俄罗斯联邦, MoscowEkaterina Soldatova
Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: katerina.soldatova95@bk.ru
ORCID iD: 0000-0001-6463-3403
PhD Student
俄罗斯联邦, MoscowVictor Tyutyunnik
Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: tioutiounnik@mail.ru
ORCID iD: 0000-0002-5830-5099
SPIN 代码: 1963-1359
Scopus 作者 ID: 56190621500
Researcher ID: B-2364-2015
Dr. Med. Sci., Professor, Leading Researcher at Center of Scientific and Clinical Researches
俄罗斯联邦, MoscowMaria Volochaeva
Academician V.I. Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: m_volochaeva@oparina4.ru
ORCID iD: 0000-0001-8953-7952
PhD, Senior Researcher at the Department of Regional Cooperation and Integration, Physician at Maternity Department No. 1
俄罗斯联邦, Moscow参考
- Nardozza L.M., Caetano A.C., Zamarian A.C., Mazzola J.B., Silva C.P., Marçal V.M. et al. Fetal growth restriction: current knowledge. Arch. Gynecol. Obstet. 2017; 295(5): 1061-77. https://dx.doi.org/10.1007/s00404-017-4341-9.
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Недостаточный рост плода, требующий предоставления медицинской помощи матери (задержка роста плода). 2022. 76с. [Ministry of Health of the Russian Federation. Clinical guidelines. Insufficient fetal growth requiring maternal medical care (fetal growth restriction). Moscow; 2022. 76p. (in Russian)].
- Oke S.L., Hardy D.B. The role of cellular stress in intrauterine growth restriction and postnatal dysmetabolism. Int. J. Mol. Sci. 2021; 22(13): 6986. https://dx.doi.org/10.3390/ijms22136986.
- Hales C.N., Barker D.J. The thrifty phenotype hypothesis. Br. Med. Bull. 2001; 60: 5-20. https://dx.doi.org/10.1093/bmb/60.1.5.
- Кан Н.Е., Солдатова Е.Е., Тютюнник В.Л., Борисова А.Г., Тезиков Ю.В., Липатов И.С., Садекова А.А., Алексеев А.А., Красный А.М. Факторы энергетического метаболизма при задержке роста плода. Акушерство и гинекология. 2024; 5: 44-52. [Kan N.E., Soldatova E.E., Tyutyunnik V.L., Borisova A.G., Tezikov Yu.V., Lipatov I.S., Sadekova A.A., Alekseev A.A., Krasnyi A.M. Factors of energy metabolism in fetal growth retardation. Obstetrics and Gynecology. 2024; (5): 44-52. (in Russian)]. https:// dx.doi.org/10.18565/aig.2024.9.
- Baggio L.L., Drucker D.J. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007; 132(6): 2131-57. https://dx.doi.org/10.1053/j.gastro.2007.03.054.
- Smith N.K., Hackett T.A., Galli A., Flynn C.R. GLP-1: molecular mechanisms and outcomes of a complex signaling system. Neurochem. Int. 2019; 128: 94-105. https://dx.doi.org/10.1016/j.neuint.2019.04.010.
- Shiraishi D., Fujiwara Y., Komohara Y., Mizuta H., Takeya M. Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation. Biochem. Biophys. Res. Commun. 2012; 425(2): 304-8. https://dx.doi.org/10.1016/j.bbrc.2012.07.086.
- Porcheray F., Viaud S., Rimaniol A.C., Léone C., Samah B., Dereuddre-Bosquet N. et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin. Exp. Immunol. 2005; 142(3): 481-9. https:// dx.doi.org/10.1111/j.1365-2249.2005.02934.x.
- Marx N., Husain M., Lehrke M., Verma S., Sattar N. GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation. 2022; 146(24): 1882-94. https://dx.doi.org/10.1161/circulationaha.122.059595.
- Рюмина И.И., Байбарина Е.Н., Нароган М.В., Маркелова М.М., Орловская И.В., Зубков В.В., Дегтярев Д.Н. Использование международных стандартов роста для оценки физического развития новорожденных и недоношенных детей. Неонатология: новости, мнения, обучение. 2023; 11(2): 48-52. [Ryumina I.I., Baibarina E.N., Narogan M.V., Markelova M.M., Orlovskaya I.V., Zubkov V.V., Degtyarev D.N. The usage of the international growth standards to assess the physical development of newborn and premature children. Neonatology: News, Opinions, Training. 2023; 11(2): 48-52. (in Russian)]. https://dx.doi.org/10.33029/2308-2402-2023-11-2-48-52.
- Кан Н.Е., Солдатова Е.Е., Тютюнник В.Л., Волочаева М.В., Садекова А.А., Красный А.М. Диагностическая значимость определения экспрессии генов энергетического метаболизма при задержке роста плода. Акушерство и гинекология. 2023; 8: 48-55. [Kan N.E., Soldatova E.E., Tyutyunnik V.L., Volochaeva M.V., Sadekova A.A., Krasnyi A.M. Diagnostic significance of determining the expression of energy metabolism genes in fetal growth retardation. Obstetrics and Gynecology. 2023; (8): 48-55 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.93.
- Bendotti G., Montefusco L., Lunati M.E., Usuelli V., Pastore I., Lazzaroni E. et al. The anti-inflammatory and immunological properties of GLP-1 receptor agonists. Pharmacol. Res. 2022; 182: 106320. https://dx.doi.org/10.1016/ j.phrs.2022.106320.
- Lee Y.S., Jun H.S. Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediators Inflamm. 2016; 2016: 3094642. https:// dx.doi.org/10.1155/2016/3094642.
- Insuela D.B.R., Carvalho V.F. Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and immunomodulatory compounds. Eur. J. Pharmacol. 2017; 812: 64-72. https://dx.doi.org/10.1016/j.ejphar.2017.07.015.
- Mehdi S.F., Pusapati S., Anwar M.S., Lohana D., Kumar P., Nandula S.A. et al. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front. Immunol. 2023; 14: 1148209. https://dx.doi.org/10.3389/fimmu.2023.1148209.
- Li Y., Glotfelty E.J., Karlsson T., Fortuno L.V, Harvey B.K., Greig N.H. The metabolite GLP-1 (9-36) is neuroprotective and anti-inflammatory in cellular models of neurodegeneration. J. Neurochem. 2021; 159(5): 867-86. https://dx.doi.org/10.1111/jnc.15521.
- Kim Chung le T., Hosaka T., Yoshida M., Harada N., Sakaue H., Sakai T. et al. Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression. Biochem. Biophys. Res. Commun. 2009; 390(3): 613-8. https://dx.doi.org/10.1016/j.bbrc.2009.10.015.
- Borg A.J., Yong H.E., Lappas M., Degrelle S.A., Keogh R.J., Da Silva-Costa F. et al. Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction. Reproduction. 2015; 149(5): 523-32. https:// dx.doi.org/10.1530/REP-14-0622.
- Yang J., Wang Y., Yang D., Ma J., Wu S., Cai Q. et al. Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs. Eur. J. Inflamm. 2021; 19: 205873922110593. https://dx.doi.org/10.1177/20587392211059362.
补充文件
