Pathophysiological impact of CXC and CX3CL1 chemokines in preeclampsia and gestational diabetes mellitus

Front Cell Dev Biol. 2023 Oct 19:11:1272536. doi: 10.3389/fcell.2023.1272536. eCollection 2023.

Abstract

Diabetes-related pathophysiological alterations and various female reproductive difficulties were common in pregnant women with gestational diabetes mellitus (GDM), who had 21.1 million live births. Preeclampsia (PE), which increases maternal and fetal morbidity and mortality, affects approximately 3%-5% of pregnancies worldwide. Nevertheless, it is unclear what triggers PE and GDM to develop. Therefore, the development of novel moderator therapy approaches is a crucial advancement. Chemokines regulate physiological defenses and maternal-fetal interaction during healthy and disturbed pregnancies. Chemokines regulate immunity, stem cell trafficking, anti-angiogenesis, and cell attraction. CXC chemokines are usually inflammatory and contribute to numerous reproductive disorders. Fractalkine (CX3CL1) may be membrane-bound or soluble. CX3CL1 aids cell survival during homeostasis and inflammation. Evidence reveals that CXC and CX3CL1 chemokines and their receptors have been the focus of therapeutic discoveries for clinical intervention due to their considerable participation in numerous biological processes. This review aims to give an overview of the functions of CXC and CX3CL1 chemokines and their receptors in the pathophysiology of PE and GDM. Finally, we examined stimulus specificity for CXC and CX3CL1 chemokine expression and synthesis in PE and GDM and preclinical and clinical trials of CXC-based PE and GDM therapies.

Keywords: CXC chemokines; fractalkine (CX3CL1); gestational diabetes mellitus; inflammation; preeclampsia; therapeutic discoveries.

Publication types

  • Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (32070671, 32270690), the COVID-19 research projects of West China Hospital Sichuan University (Grant no. HX-2019-nCoV-057) as well as the regional innovation cooperation between Sichuan and Guangxi Provinces (2020YFQ0019).