Is leukemia inhibitory factor involved in the pathogenesis of preeclampsia?
Is leukemia inhibitory factor involved in the pathogenesis of preeclampsia?
Mehrnaz Abdolalian,1Parvinsadat Eslamnik,2,*
1. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran 2. Department of Obstetrics and Gynecology, School of Medicine, Yasuj University of Medical Science, Yasuj, Iran.
Introduction: Preeclampsia (PE) is a pregnancy-specific disorder characterized by high blood pressure after the 20th week of pregnancy and other organ disorders such as kidney failure, liver involvement, neurological and hematological complications in the mother's body. The etiology and pathogenesis of this disorder remain unknown. Leukemia inhibitory factor (LIF) is a secretory glycoprotein of the IL-6 super family. LIF has various functions in fetal development, embryo implantation in the uterus and inflammatory responses. Due to the role of this factor in the process of pregnancy and fetal development, In this study, we first reviewed the role of LIF in the pathogenesis of PE through PE-related pathways such as inflammation, hypertension and endothelial dysfunction.
Methods: This review article is a study of PubMed content from 1980 to 2020. The keywords used in this search were -Leukemia Inhibitory factor-, -Preeclampsia-, -Endothelial Cell Dysfunction-, -Inflammation- and --Hypertension-.
Results: JAK / STAT is one of the pathways activated by LIF .Binding of LIF to LIF receptor (LIFR) via the JAK/STAT3 signaling pathway and up-regulation of MMP-14 increases endoglin production. Increased endoglin levels due to increased MMP-14 expression are involved in Endothelial dysfunction. Damage to the maternal endothelium has been considered as the main hallmark of PE . Phosphorylation of STAT3 by binding LIF to LIFR leads to abnormal expression of ICAM-1 and VCAM-1 on the surface of Endothelial cells, leukocyte excitation, induction of inflammation and endothelial dysfunction. Binding LIF to LIFR via the JAK / STAT pathway also activates RhoA. RhoA inhibits eNOS(endothelial nitric oxide synthase) phosphorylation and decreases NO (nitric oxide) production. If the production of NO (as a vasodilator) is impaired, it is involved in the pathogenesis of many diseases such as hypertension and PE. The level of angiogenic factors such as VEGF(vascular endothelial growth factor) decreases in PE. There is evidence for the effect of LIF on decreased VEGF gene expression.
Conclusion: Given that PE is one of the leading causes of mortality during pregnancy in pregnant women, the study of factors affecting the pathogenesis of PE is very effective in achieving therapeutic methods. It seems that the binding of LIF to LIFR can induce inflammatory responses, hypertension and endothelial dysfunction (as the main hallmark of PE) by inducing different signaling pathways, especially the JAK/STAT3 pathway.