Research progress of olfactomedin 4 in regulating immune inflammatory response

doi:10.16352/j.issn.1001-6325.2026.04.0587

Abstract

Abstract: Olfactomedin 4 (OLFM4) is an olfactomedin domain family glycoprotein that plays an important role in immune regulation, cell apoptosis and anti-microbial infection. It can affect the activation, migration and apoptosis of immune cells, epithelial cells and tumor cells. OLFM4 has important relationships with multiple signal transduction pathway factors, including β-catenin,NF-κB,STAT3,MAPK and cGAS-STING. In recent years, with advancing research on OLFM4, it has been found that the abnormal expression of OLFM4 is closely related to the prognosis of infectious diseases, tumor development and a variety of inflammatory diseases, which suggests that OLFM4 is a potential early biomarker for diseases and a potential target for clinical therapeutics.

Key words: olfactomedin 4, immune regulation, inflammatory response, signaling pathway

CLC Number:

R392

WU Yi, XIA Likun. Research progress of olfactomedin 4 in regulating immune inflammatory response[J]. Basic & Clinical Medicine, 2026, 46(4): 587-591.

References

[1] Zhang J, Liu WL, Tang DC, et al. Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development[J]. Gene, 2002, 283: 83-93.doi:10.1016/s0378-1119(01)00763-6.
[2] Liu W, Chen L, Zhu J, et al. The glycoprotein hGC-1 binds to cadherin and lectins[J]. Exp Cell Res, 2006, 312: 1785-1797.doi:10.1016/j.yexcr.2006.02.011.
[3] Zou Y, Kamada N, Seong SY, et al. CD115(-) monocytic myeloid-derived suppressor cells are precursors of OLFM4(high) polymorphonuclear myeloid-derived suppressor cells[J]. Commun Biol, 2023, 6: 272.doi:10.1038/s42003-023-04650-3.
[4] Chen Z, Zhang X, Xing Z, et al. OLFM4 deficiency delays the progression of colitis to colorectal cancer by abrogating PMN-MDSCs recruitment[J]. Oncogene, 2022, 41: 3131-3150.doi:10.1038/s41388-022-02324-8.
[5] Jabeen A, Ahmad N, Raza K. Global gene expression and docking profiling of COVID-19 infection[J]. Front Genet, 2022, 13: 870836.doi:10.3389/fgene.2022.870836.
[6] Xu K, Zheng P, Zhao S, et al. LRFN5 and OLFM4 as novel potential biomarkers for major depressive disorder: a pilot study[J]. Transl Psychiatry, 2023, 13: 188.doi:10.1038/s41398-023-02490-7.
[7] Zhang F, Li Y, Xi Y, et al. Qinbaohong Zhike oral liquid attenuates LPS-induced acute lung injury in immature rats by inhibiting OLFM4[J]. Oxid Med Cell Longev, 2022, 2022: 7272371.doi:10.1155/2022/7272371.
[8] Vandenberghe-Durr S, Gilliet M, Di Domizio J. OLFM4 regulates the antimicrobial and DNA binding activity of neutrophil cationic proteins[J]. Cell Rep, 2024, 43: 114863.doi:10.1016/j.celrep.2024.114863.
[9] Novak T, Crawford JC, Hahn G, et al. Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza[J]. Front Immunol, 2023, 14: 1220028.doi:10.3389/fimmu.2023.1220028.
[10] 王启源, 姬文兰, 虞秀锋. 嗅素蛋白4对卡介苗诱导巨噬细胞凋亡和细菌胞内生存率的影响[J]. 检验医学, 2020, 35: 818-822.doi:10.3969/j.issn.1673-8640.2020.08.017.
[11] He H, Chen S, Yu Y, et al. Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer[J]. Gut, 2024, 73: 1529-1542.doi:10.1136/gutjnl-2023-331773.
[12] Baek BS, Park H, Choi JW, et al. Dendritic cells pulsed with penetratin-OLFM4 inhibit the growth and metastasis of melanoma in mice[J]. Biomed Pharmacother, 2024, 177: 117083.doi:10.1016/j.biopha.2024.117083.
[13] Wei H, Li W, Zeng L, et al. OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3beta/beta-catenin pathway[J]. Mol Cancer, 2024, 23: 124.doi:10.1186/s12943-024-02016-9.
[14] Huang J, Xu Z, Jiao J, et al. Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury[J]. Bioact Mater, 2023, 30: 1-14.doi:10.1016/j.bioactmat.2023.07.001.
[15] Ashizawa Y, Kuboki S, Nojima H, et al. OLFM4 enhances STAT3 activation and promotes tumor progres-sion by inhibiting GRIM19 expression in human hepatocellular carcinoma[J]. Hepatol Commun, 2019, 3: 954-970.doi:10.1002/hep4.1361.
[16] Tang Z, Wei C, Deng X, et al. Serum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected with Clonorchis sinensis[J]. Front Immunol, 2024, 15: 1489077.doi:10.3389/fimmu.2024.1489077.
[17] Liu W, Li H, Aerbajinai W, et al. OLFM4-RET fusion is an oncogenic driver in small intestine adenocarcinoma[J]. Oncogene, 2022, 41: 72-82.doi:10.1038/s41388-021-02072-1.
[18] Xing Z, Li X, He J, et al. OLFM4 modulates intestinal inflammation by promoting IL-22(+)ILC3 in the gut[J]. Commun Biol, 2024, 7: 914.doi:10.1038/s42003-024-06601-y.
[19] Chen C, Xu P. Cellular functions of cGAS-STING signaling[J]. Trends Cell Biol, 2023, 33: 630-648.doi:10.1016/j.tcb.2022.11.001.
[20] Wen F, Han Y, Zhang H, et al. Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression[J]. Nat Commun, 2024, 15: 10543.doi:10.1038/s41467-024-54850-6.