In a bioinformatics study in 2002 (Walker and Volkmuth, 2002), Walker and Volkmuth firstly identified eight genes that co-expressed with a set of genes that mediated matrix remodeling and cell adhesion (e.g., collagens, matrix metalloproteinases, etc.), and named them MXRA1-MXRA8 (matrix remodeling associated genes). Although there were no sequence homologies among these eight MXRAs, later studies reported that several of them affected a variety of critical physiological and pathological processes involving matrix remodeling (Bernau et al., 2017, Kakinuma et al., 2009, Nativel et al., 2019, Pignatelli et al., 2012, Poveda et al., 2017, Song et al., 2019, Wang et al., 2020). Scattered data mentioned that MXRA7 was overexpressed in childhood acute lymphoblastic leukemia and in ovarian endometriomas (Flotho et al., 2006, Veiga-Castelli et al., 2010). In a continuing effort to characterize the functions of MXRA7, our lab found that MXRA7 was involved in inflammation, tissue injury and cell differentiation (Jia et al., 2017, Lin et al., 2018, Ning et al., 2018, Sun et al., 2023a, Sun et al., 2023b, Zhou et al., 2019). In murine inflammatory corneal neovascularization models, MXRA7 mRNA levels manifested a dynamic change, which was opposite to the levels of matrix metalloproteinases that mediated corneal neovascularization (Jia et al., 2017). Ning et al. found that MXRA7 might act as a negative modulator in psoriasis development when propsoriatic factors were present, possibly via expression alteration or redistribution of MXRA7 in keratinocytes (Ning et al., 2018). In a carbon tetrachloride-induced acute liver injury mouse model, MXRA7 regulated the liver tissue injury through mediating the inflammation response and matrix remodeling processes (Lin et al., 2018). Moreover, we also found that MXRA7 affected cell differentiation, including the differentiation of bone marrow mesenchymal stem cells (BMSCs) towards osteoblasts (Zhou et al., 2019), megakaryocyte differentiation (Sun et al., 2023b), and acute promyelocytic leukemia cell differentiation (Sun et al., 2023a).

Monocytes and macrophages are critical in mediating innate immune responses and inflammatory responses (Pinto et al., 2021). Monocytes can migrate to the tissues and sites of inflammation and differentiate into macrophages for function (Coillard and Segura, 2019, Shi and Pamer, 2011). Previous studies reported that matrix proteins could modulate monocyte-to-macrophage differentiation (Jacob et al., 2002, Sudhakaran et al., 2007). As a matrix remolding protein, the effect of MXRA7 on monocyte-to-macrophage differentiation remains to be explored. In this study, we used human THP-1 cell line to investigate the hypothetical role of MXRA7 in the differentiation of monocyte to macrophages. We demonstrated that MXRA7 was a regulator of THP-1 cell behavior and differentiation, which indicated an important role of MXRA7 in monocyte-to-macrophages differentiation.