CTRP6 regulates M1 macrophage polarization via the PPAR-γ/NF-κB pathway and reprogramming glycolysis in recurrent spontaneous abortion

Sisi Yan; Jinli Ding; Zehao Wang; Feng Zhang; Jianan Li; Yi Zhang; Shujuan Wu; Lian Yang; Xiangli Pang; Yan Zhang; Jing Yang

doi:10.1016/j.intimp.2023.110840

CTRP6 regulates M1 macrophage polarization via the PPAR-γ/NF-κB pathway and reprogramming glycolysis in recurrent spontaneous abortion

Int Immunopharmacol. 2023 Nov;124(Pt A):110840. doi: 10.1016/j.intimp.2023.110840. Epub 2023 Sep 9.

Authors

Sisi Yan¹, Jinli Ding¹, Zehao Wang¹, Feng Zhang¹, Jianan Li¹, Yi Zhang¹, Shujuan Wu¹, Lian Yang¹, Xiangli Pang¹, Yan Zhang², Jing Yang³

Affiliations

¹ Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, China.
² Department of Clinical Laboratory, Renmin Hospital of Wuhan University, WuHan, HuBei, China. Electronic address: peneyyan@whu.edu.cn.
³ Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, China. Electronic address: dryangjing@whu.edu.cn.

PMID: 37696144
DOI: 10.1016/j.intimp.2023.110840

Abstract

Aberrant polarization and functions of decidual macrophages are closely related to recurrent spontaneous abortion (RSA). C1q/tumor necrosis factor-related protein 6 (CTRP6) is a member of the adiponectin paralog family, and plays indispensable roles in inflammation, glucose uptake and tumor metastasis. However, the regulatory effect of CTRP6 on macrophage polarization and glycolysis in RSA and the underlying mechanisms have not been fully elucidated. In the present study, we first found that CTRP6 expression was positively correlated with the M1 macrophage marker (CD86) in decidual tissues by dual immunofluorescence analysis. In vitro experiments indicated that CTRP6 could facilitate M1 macrophage activation through the PPAR-γ/NF-κB pathway and manipulate the glycolysis of macrophages. Notably, in addition to silencing CTRP6, treatment with a PPAR-γ agonist (GW1929) inhibited M1 macrophage polarization and rescued embryo absorption in vivo. Taken together, these results identify previously unrevealed functions of CTRP6 in macrophage transformation during RSA.

Keywords: CTRP6; Glycolysis; Macrophage polarization; Recurrent spontaneous abortion.