Expression of HMGB1 and NF-κB in Fetal Membranes of Premature Rupture of Membranes
Abstract
Background: Inflammation, either sterile or infection-related, may lead to premature rupture of membranes (PROM). The non-histone nuclear proteins, high mobility group box-1 (HMGB1), and nuclear factor kappa-B (NF-κB) transcription factors have been extensively investigated in many disorders involving inflammatory reactions. This study aimed to determine the expression of HMGB1 and NF-κB in fetal membranes of PROM compared with non-PROM.
Methods: This study was an analytical observational study with a case-control design, performed from November 2021 to January 2022, including 40 fetal membrane samples (20 PROM and 20 non-PROM), which were obtained from pregnant women treated in the emergency unit of a hospital in Surabaya from August to November 2019 using the non-probability sampling method. The HMGB1 and NF-κB expressions were examined using the immunohistochemical method and further viewed under a light microscope (400x magnification), then assessed by Image-J software. The values were then compared between PROM and non-PROM, and analyzed using the Mann-Whitney U test.
Results: There was a significant difference (p<0.001) in the expression of HMGB1 and NF-κB in PROM and non-PROM for HMGB1 45.86± 14.21% vs. 8.50± 5.66% expression/mm2; and NF-κB 33.47±5.45% vs. 7.29±4.90% expression/mm2, respectively.
Conclusions: PROM groups have significantly higher expression of HMGB1 and NF-κB s, indicating their higher activity and contribution to PROM.
Keywords
Full Text:
PDFReferences
- World Health Organization. New global estimates on preterm birth published [Internet]. Geneva:WHO. 2018 [cited 2022 July 5]. Available from: https://www.who.int/news/item/17-11-2018-new-global-estimates-on-preterm-birth-published.
- Halimi Asl AA, Safari S, Parvareshi Hamrah M. Epidemiology and related risk factors of preterm labor as an obstetrics emergency. Emerg (Tehran). 2017;5(1):e3.
- Assefa NE, Berhe H, Girma F, Berhe K, Berhe YZ, Gebrehet G, et al. Risk factors of premature rupture of membranes in public hospitals at Mekele city, Tigray, a case control study. BMC Pregnancy Childbirth. 2018;18(1):386.
- Verbruggen SW, Oyen ML, Phillips ATM, Nowlan NC. Function and failure of the fetal membrane: modelling the mechanics of the chorion and amnion. PLoS One. 2017;12(3):e0171588.
- Nunes V, Cross J, Speich JE, Morgan DR, Strauss JF 3rd, Ramus RM. Fetal membrane imaging and the prediction of preterm birth: a systematic review, current issues, and future directions. BMC Pregnancy Childbirth. 2016;16(1):387.
- Lee S-A, Kwak MS, Kim S, Shin J-S. The role of high mobility group box 1 in innate immunity. Yonsei Med J. 2014;55(5):1165–76.
- Yang H, Wang H, Andersson U. Targeting inflammation driven by HMGB1. Front Immunol. 2020;11:484.
- Bredeson S, Papaconstantinou J, Deford JH, Kechichian T, Syed TA, Saade GR, et al. HMGB1 promotes a p38MAPK associated non-infectious inflammatory response pathway in human fetal membranes. PLoS One. 2014;9(12):e113799.
- Yan H, Zhu L, Zhang Z, Li H, Li P, Wang Y, et al. HMGB1-RAGE signaling pathway in pPROM. Taiwan J Obstet Gynecol. 2018;57(2):211–6.
- Menon R, Behnia F, Polettini J, Saade GR, Campisi J, Velarde M. Placental membrane aging and HMGB1 signaling associated with human parturition. Aging (Albany NY). 2016;8(2):216–30.
- Chavez FG, Correa D, Navarrete-Meneses P, Cancino-Diaz JC, Cancino-Diaz ME, Rodrıguez-Martinez S. NF-kB and its regulators during pregnancy. Front Immunol. 2021;12:679106.
- Romero R, Chaiworapongsa T, Savasa ZA, Xu Y, Hussein Y, Dong Z, et al. Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1. J Matern Fetal Neonatal Med. 2011;24(12):1444–55.
- Sheller-Miller S, Urrabaz-Garza R, Saade G, Menon R. Damage-associated molecular pattern markers HMGB1 and cell free fetal telomere fragments in oxidative-stressed amnion epithelial cell-derived exosomes. J Reprod Immunol. 2017;123:3–11.
- Padron JG, Reis CAS, Kendal-Wright CE. The role of danger associated molecular patterns in human fetal membrane weakening. Front Physiol. 2020;11(602).
- Davalos AR, Kawahara M, Malhotra GK, Schaum N, Huang J, Ved U, et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol. 2013;201(4):613–29.
- He Z-W, Qin Y-H, Wang Z-W, Chen Y, Shen Q, Dai S-M. HMGB1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial fibroblasts via p38 MAPK and NF-κB signaling pathways. Mediators Inflamm. 2013;2013:596716.
- Lim S, MacIntyre DA, Lee YS, Khanjani S, Terzidou V, Teoh TG, et al. Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes. PLoS One. 2012;7(4):e34707.
- Wang F, Wang Y, Wang R, Qiu H, Chen L. Predictive value of maternal serum NF-κB p65 and sTREM-1 for subclinical chorioamnionitis in premature rupture of membranes. Am J Reprod Immunol. 2016;76(3):217–23.
- Erşahin SS. The comparison of amniotic fluid nuclear factor-kappa B levels in pregnant women who underwent cesarean section or normal vaginal labor. Perinat J. 2021;29(1):8–12.
- Strauss JF 3rd. Extracellular matrix dynamics and fetal membrane rupture. Reprod Sci. 2013;20(2):140–53.
- Zenerino C, Nuzzo AM, Giuffrida D, Biolcati M, Zicari A, Todros T, et al. The HMGB1/RAGE pro-inflammatory axis in the human placenta: modulating effect of low molecular weight heparin. Molecules. 2017;22(11):1997.
- Liang W-J, Yang H-W, Liu H-N, Qian W, Chen X-L. HMGB1 upregulates NF-kB by inhibiting IKB-α and associates with diabetic retinopathy. Life Sci. 2020;241:117146.
- Mogami H, Kishore AH, Akgul Y, Word RA. Healing of preterm ruptured fetal membranes. Sci Rep. 2017;7(1):13139.
- Fan H, Tang H-B, Chen Z, Wang H-Q, Zhang L, Jiang Y, et al. Inhibiting HMGB1-RAGE axis prevents pro_inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury. J Neuroinflammation. 2020;17(1):295.
- Hazlett LD, McClellan S, Somayajulu M, Bessert D. Targeting inflammation driven by HMGB1 in bacterial keratitis—a review. Pathogens. 2021;10(10):1235.
- Yu H, Lin L, Zhang Z, Zhang H, Hu H. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther. 2020;5(1):209.
DOI: https://doi.org/10.15850/amj.v10n4.2911
Article Metrics
Abstract view : 227 timesPDF - 113 times
This Journal indexed by
AMJ is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
View My Stats