본문 바로가기
KERD
논문KCI 등재

RAR-Related Orphan Receptor: An Accelerated Preeclampsia Progression by Activating the JAK/STAT3 Pathway

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류의학일반

초록

Purpose: To investigate the effect and underlying mechanism of RAR related orphan receptor A (RORA) on preeclampsia (PE). Materials and Methods: Differentially expressed genes (DEGs) in four datasets were obtained by using the Venn diagram method. RORA mRNA and protein expressions were detected by qRT-PCR, western blot, and immunohistochemistry. HTR-8/SVneocell viability, proliferation, invasion, migration, and angiogenesis were detected by CCK-8 assay, EdU assay, Transwell, woundhealing assay, and tube formation assay, respectively. The concentration of Ang-1 in cells was assessed using available ELISA kit. Epithelial-mesenchymal transition, proliferation, and angiogenesis-related proteins were detected by western blot. GSEA analysiswere performed for common DEGs, and the expression of enriched pathway-related proteins was also detected. Results: The expression of RORA was increased in PE tissue and HTR-8/SVneo cells. Silencing RORA could promote the migration,invasion, epithelial-mesenchymal transition, proliferation, and angiogenesis of hypoxia-treated HTR-8/SVneo cells. Mechanistically,RORA contributed to the deterioration of PE by activating the JAK2/STAT3 signaling pathway to promote cell proliferation,migration, invasion, and angiogenesis. Conclusion: RORA was up-regulated in PE and affected HTR-8/SVneo cell proliferation, invasion, migration, apoptosis, and angiogenesisvia the JAK2/STAT3 signaling pathway. This provided a novel strategy for the prevention and treatment of PE.

Abstract

Purpose: To investigate the effect and underlying mechanism of RAR related orphan receptor A (RORA) on preeclampsia (PE). Materials and Methods: Differentially expressed genes (DEGs) in four datasets were obtained by using the Venn diagram method. RORA mRNA and protein expressions were detected by qRT-PCR, western blot, and immunohistochemistry. HTR-8/SVneocell viability, proliferation, invasion, migration, and angiogenesis were detected by CCK-8 assay, EdU assay, Transwell, woundhealing assay, and tube formation assay, respectively. The concentration of Ang-1 in cells was assessed using available ELISA kit. Epithelial-mesenchymal transition, proliferation, and angiogenesis-related proteins were detected by western blot. GSEA analysiswere performed for common DEGs, and the expression of enriched pathway-related proteins was also detected. Results: The expression of RORA was increased in PE tissue and HTR-8/SVneo cells. Silencing RORA could promote the migration,invasion, epithelial-mesenchymal transition, proliferation, and angiogenesis of hypoxia-treated HTR-8/SVneo cells. Mechanistically,RORA contributed to the deterioration of PE by activating the JAK2/STAT3 signaling pathway to promote cell proliferation,migration, invasion, and angiogenesis. Conclusion: RORA was up-regulated in PE and affected HTR-8/SVneo cell proliferation, invasion, migration, apoptosis, and angiogenesisvia the JAK2/STAT3 signaling pathway. This provided a novel strategy for the prevention and treatment of PE.

참고문헌 (39)

  1. Kurtz WS, "Retinal artery and vein thrombotic occlusion during pregnancy : markers for familial thrombophilia and adverse pregnancy outcomes", Clin Ophthalmol, 10, pp.935~938 (2016)
  2. Zhang M, "Regulatory mechanism of miR-525-5p in over-invasion of trophoblast", J Obstet Gynaecol Res, 47, pp.679~688 (2021)
  3. Whitehead CL, "EGFL7 gene expression is regulated by hypoxia in trophoblast and altered in the plasma of patients with early preeclampsia", Pregnancy Hypertens, 14, pp.115~120 (2018)
  4. Zhou C, "Role of oxygen in fetoplacental endothelial responses: hypoxia, physiological normoxia, or hyperoxia?", Am J Physiol Cell Physiol, 318, pp.C943~C953 (2020)
  5. Steegers EA, "Pre-eclampsia", Lancet, 376, pp.631~644 (2010)
  6. Backes CH, "Maternal preeclampsia and neonatal outcomes", J Pregnancy, 2011, pp.214365~ (2011)
  7. Solt LA, "The REV-ERBs and RORs : molecular links between circadian rhythms and lipid homeostasis", Future Med Chem, 3, pp.623~638 (2011)
  8. Li H, "Retinoic acid receptor-related orphan receptor RORα regulates differentiation and survival of keratinocytes during hypoxia", J Cell Physiol, 233, pp.641~650 (2018)
  9. Chauvet C, "Retinoic acid receptor-related orphan receptor(ROR)α4 is the predominant isoform of the nuclear receptor RORα in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cells", Biochem J, 364, pp.449~456 (2002)
  10. Farahani S, "RAR-related orphan receptor A : one gene with multiple functions related to migraine", CNS Neurosci Ther, 26, pp.1315~1321 (2020)
  11. Cai J, "The orphan nuclear receptor RORα is a potential endogenous protector in renal ischemia", reperfusion injury, 2019, pp.33, 5704~5715
  12. Huang H, "Melatonin prevents endothelial dysfunction in SLE by activating the nuclear receptor retinoic acid-related orphan receptor-α", Int Immunopharmacol, 83, pp.106365~ (2020)
  13. Miller MW, "The retinoid-related orphan receptor alpha(RORA)gene and fear-related psychopathology", J Affect Disord, 151, pp.702~708 (2013)
  14. Yang Z, "Guidelines for diagnosis and treatment of Hypertensive Diseases during Pregnancy(2015)", Chin J Obstet Gynecol, 50, pp.721~728 (2015)
  15. Gerasimova EM, "Protein misfolding during pregnancy : new approaches to preeclampsia diagnostics", Int J Mol Sci, 20, pp.6183~ (2019)
  16. Zhang M, "Preeclampsia among African American pregnant women : an update on prevalence, complications, etiology, and biomarkers", Obstet Gynecol Surv, 75, pp.111~120 (2020)
  17. Broz´yna AA, "On the relationship between VDR, RORα and RORγ receptors expression and HIF1-α levels in human melanomas", Exp Dermatol, 28, pp.1036~1043 (2019)
  18. Qiu C, "Circadian clock-related genetic risk scores and risk of placental abruption", Placenta, 36, pp.1480~1486 (2015)
  19. Qiu C, "Placental genetic variations in circadian clock-related genes increase the risk of placental abruption", Int J Mol Epidemiol Genet, 7, pp.32~40 (2016)
  20. Behnia F, "Fetal DNA methylation of autism spectrum disorders candidate genes : association with spontaneous preterm birth", Am J Obstet Gynecol, 212, pp.533.e1~533.e9 (2015)
  21. Malik A, "Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8", SVneo cell invasion, 2017, pp.12, e0178269~
  22. Gupta SK, "Cell signaling pathways involved during invasion and syncytialization of trophoblast cells", Am J Reprod Immunol, 75, pp.361~371 (2016)
  23. Uchikura Y, "Extranuclear translocation of high-mobility group A1 reduces the invasion of extravillous trophoblasts involved in the pathogenesis of preeclampsia : new aspect of high-mobility group A1", Reprod Sci, 24, pp.1630~1638 (2017)
  24. Ospina-Prieto S, "miR-134 regulates invasion and proliferation in HTR-8", SVneo cells, 2014, pp.35, A104~A105
  25. Ge H, "Interleukin-27inhibits trophoblast cell invasion and migration by affecting the epithelial-mesenchymal transition in preeclampsia", Reprod Sci, 26, pp.928~938 (2019)
  26. Shen XY, "CircTRNC18 inhibits trophoblast cell migration and epithelialmesenchymal transition by regulating miR-762", Grhl2 pathway in pre-eclampsia, 2019, pp.16, 1565~1573
  27. Zou Y, "Resveratrol promotes trophoblast invasion in pre-eclampsia by inducing epithelial-mesenchymal transition", J Cell Mol Med, 23, pp.2702~2710 (2019)
  28. Lyall F, "Human trophoblast invasion and spiral artery transformation : the role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction", Am J Pathol, 158, pp.1713~1721 (2001)
  29. Weiss G, "The trophoblast plug during early pregnancy : a deeper insight", Histochem Cell Biol, 146, pp.749~756 (2016)
  30. Li T, "Nesfatin-1 promotes proliferation, migration and invasion of HTR-8", SVneo Trophoblast cells and inhibits oxidative stress via activation of PI3K, mTOR and AKT, pp.GSK3β pathway, Reprod Sci[DOI]
  31. Hemmatzadeh M, "MicroRNAs : small molecules with a large impact on pre-eclampsia", J Cell Physiol, 235, pp.3235~3248 (2020)
  32. Chen JX, "HSP90 and Akt modulate Ang-1-induced angiogenesis via NO in coronary artery endothelium", J Appl Physiol(1985), 96, pp.612~620 (2004)
  33. Kowshik J, "Astaxanthin inhibits JAK", STAT-3 signaling to abrogate cell proliferation, invasion and angiogenesis in a hamster model of oral cancer, 2014, pp.9, e109114~
  34. Zeng Y, "miR-150-5p mediates extravillous trophoblast cell migration and angiogenesis functions by regulating VEGF and MMP9", Placenta, 93, pp.94~100 (2020)
  35. Dodington DW, "JAK", STAT–emerging players in metabolism, 2018, pp.29, 55~65
  36. Qu H, "HIF‑3α affects preeclampsia development by regulating EVT growth via activation of the Flt‑1", JAK, Mol Med Rep, pp.2021, 23[DOI]
  37. Tang J, "MiR-125b participates in the occurrence of preeclampsia by regulating the migration and invasion of extravillous trophoblastic cells through STAT3 signaling pathway", J Recept Signal Transduct Res, 41, pp.202~208 (2021)
  38. Wang D, "Stat3phosphorylation is required for embryonic stem cells ground state maintenance in 2i culture media", Oncotarget, 8, pp.31227~31237 (2017)
  39. Xu C, "Hypoxia-induced activation of JAK", STAT3 signaling pathway promotes trophoblast cell viability and angiogenesis in preeclampsia, 2017, pp.23, 4909~4917

관련 논문AI추천

Expression and Localization of COMMD1 Proteins in Human Placentas from Women with Preeclampsia권한성, 김수녕, 박승화, 손인숙, 황한성연세대학교의과대학 · Yonsei Medical Journal2013 · 제54권 제2호Alleviation of preeclampsia-like symptoms through PlGF and eNOS regulation by hypoxia- and NF-κB-responsive miR-214-3p deletion김지윤, 심성보, 이정형, Byeon Junyoung, Hong Jungwoo, Kim Suji, Kim Young-Myeong, Kwon Jisoo, Kwon Young-Guen, Ryoo Sungwoo생화학분자생물학회 · Experimental and Molecular Medicine2024 · 제56권 STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9강희경, 고현선, 김아영, 김호식, 박병준, 박인양, 신종철, 최세경연세대학교의과대학 · Yonsei Medical Journal2016 · 제57권 제3호IL-23 Inhibits Trophoblast Proliferation, Migration, and EMT via Activating p38 MAPK Signaling Pathway to Promote Recurrent Spontaneous AbortionDeng Shaojie, He Shan, Jiang Shaoyan, Liu Dayan, Ma Fei, Ning Yan한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2022 · 제32권 제6호Correlation of VEGF, HIF-1α, and MMP2 expression in placental villi among patients with recurrent spontaneous abortionXiaofeng Zhang, Xiaolin Hou, Yage Wang, Yan Feng, Yaru Ju대한산부인과학회 · Obstetrics & Gynecology Science2025 · 제68권 제5호Associations between Maternal sFlt-1/PlGF Ratio and Perinatal and Neonatal Outcomes in Newborns Born to Mothers with PreeclampsiaChang Won Choi, Hyo Ju Yang, Hyun Soo Kim, Soo Yeon Lim, Younghwa Jung대한신생아학회 · Neonatal medicine2023 · 제30권 제3호

이 간행물의 다른 논문 (12건)