MXRA7 is involved in monocyte-to-macrophage differentiation

Zhenjiang Sun; Peng Ke; Ying Shen; Kunpeng Ma; Benfang Wang; Dandan Lin; Yiqiang Wang

doi:10.1016/j.molimm.2024.05.001

MXRA7 is involved in monocyte-to-macrophage differentiation

Mol Immunol. 2024 May 11:171:12-21. doi: 10.1016/j.molimm.2024.05.001. Online ahead of print.

Authors

Zhenjiang Sun¹, Peng Ke¹, Ying Shen¹, Kunpeng Ma², Benfang Wang², Dandan Lin³, Yiqiang Wang⁴

Affiliations

¹ Institute of Blood and Marrow Transplantation, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou Medical College, Soochow University, Suzhou 215006, China.
² MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Medical College, Soochow University, Suzhou 215007, China.
³ Institute of Blood and Marrow Transplantation, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou Medical College, Soochow University, Suzhou 215006, China. Electronic address: lindandan@suda.edu.cn.
⁴ MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Medical College, Soochow University, Suzhou 215007, China; Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China. Electronic address: yiqiang.wang@xjtlu.edu.cn.

PMID: 38735126
DOI: 10.1016/j.molimm.2024.05.001

Abstract

Macrophages are critical in mediating immune and inflammatory responses, while monocyte-to-macrophage differentiation is one of the main macrophage resources that involves various matrix proteins. Matrix remodeling associated 7 (MXRA7) was recently discovered to affect a variety of physiological and pathological processes related to matrix biology. In the present study, we investigated the role of MXRA7 in monocyte-to-macrophage differentiation in vitro. We found that knockdown of MXRA7 inhibited the proliferation of THP-1 human monocytic cells. Knockdown of MXRA7 increased the adhesion ability of THP-1 cells through upregulation the expression of adhesion molecules VCAM-1 and ICAM1. Knockdown of MXRA7 alone could promoted the differentiation of THP-1 cells to macrophages. Furthermore, the MXRA7-knockdown THP-1 cells produced a more significant upregulation pattern with M1-type cytokines (TNF-α, IL-1β and IL-6) than with those M2-type molecules (TGF-β1 and IL-1RA) upon PMA stimulation, indicating that knockdown of MXRA7 facilitated THP-1 cells differentiation toward M1 macrophages. RNA sequencing analysis revealed the potential biological roles of MXRA7 in cell adhesion, macrophage and monocyte differentiation. Moreover, MXRA7 knockdown promoted the expression of NF-κB p52/p100, while PMA stimulation could increase the expression of NF-κB p52/p100 and activating MAPK signaling pathways in MXRA7 knockdown cells. In conclusion, MXRA7 affected the differentiation of THP-1 cells toward macrophages possibly through NF-κB signaling pathways.

Keywords: Cell adhesion; Extracellular matrix; MXRA7; Macrophages; Monocyte differentiation.