SOCS1 improves abnormal IgA galactosylation in IgA nephropathy by regulating the TLR9/MyD88 pathway

Cheung CK, Alexander S, Reich HN, Selvaskandan H, Zhang H, Barratt J. The pathogenesis of IgA nephropathy and implications for treatment. Nat Rev Nephrol. 2025;21(1):9–23. https://doi.org/10.1038/s41581-024-00885-3.

Article  CAS  PubMed  Google Scholar 

Stamellou E, Seikrit C, Tang SCW, Boor P, Tesař V, Floege J, et al. IgA nephropathy. Nat Rev Disease Primers. 2023;9(1):67. https://doi.org/10.1038/s41572-023-00476-9.

Suzuki H, Novak J. Special issue: new insights into the pathogenesis and therapies of IgA nephropathy. J Clin Med. 2022;11(15). https://doi.org/10.3390/jcm11154378.

Zhu Y, He H, Sun W, Wu J, Xiao Y, Peng Y, et al. IgA nephropathy: gut microbiome regulates the production of hypoglycosilated IgA1 via the TLR4 signaling pathway. Nephrol, Dialysis, Transp : Off Publ Eur Dial Transplant Assoc - Eur Renal Assoc. 2024;39(10):1624–41. https://doi.org/10.1093/ndt/gfae052.

Article  CAS  Google Scholar 

Li GS, Zhang H, Lv JC, Shen Y, Wang HY. Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy. Kidney Int. 2007;71(5):448–53. https://doi.org/10.1038/sj.ki.5002088.

Article  CAS  PubMed  Google Scholar 

Novak J, Barratt J, Julian BA, Renfrow MB. Aberrant glycosylation of the IgA1 molecule in IgA nephropathy. Semin Nephrol. 2018;38(5):461–76. https://doi.org/10.1016/j.semnephrol.2018.05.016.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bidgood GM, Keating N, Doggett K, Nicholson SE. SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity. Front Immunol. 2024;15:1419951. https://doi.org/10.3389/fimmu.2024.1419951.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lockwood KC, Lear TB, Rajbhandari S, McKelvey AC, Dunn SR, Boudreau ÁN, et al. KIAA0317 regulates SOCS1 stability to ameliorate colonic inflammation. FEBS J. 2023;290(15):3802–11. https://doi.org/10.1111/febs.16780.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang J, Li H, Yu JP, Wang SE, Ren XB. Role of SOCS1 in tumor progression and therapeutic application. Int J Cancer. 2012;130(9):1971–80. https://doi.org/10.1002/ijc.27318.

Article  CAS  PubMed  Google Scholar 

Sheikh T, Sen E. p53 affects epigenetic signature on SOCS1 promoter in response to TLR4 inhibition. Cytokine. 2021;140:155418. https://doi.org/10.1016/j.cyto.2020.155418.

Article  CAS  PubMed  Google Scholar 

Heeg K, Dalpke A. TLR-induced negative regulatory circuits: role of suppressor of cytokine signaling (SOCS) proteins in innate immunity. Vaccine. 2003;21(Suppl 2):S61–7. https://doi.org/10.1016/s0264-410x(03)00202-0.

Article  PubMed  Google Scholar 

Yu CF, Peng WM, Schlee M, Barchet W, Eis-Hübinger AM, Kolanus W, et al. SOCS1 and SOCS3 target IRF7 degradation to suppress TLR7-mediated type I IFN production of human plasmacytoid dendritic cells. J Immunol (Baltimore, Md: 1950). 2018;200(12):4024–35. https://doi.org/10.4049/jimmunol.1700510.

Article  CAS  Google Scholar 

Liu H, Wang W, Liu C. Increased expression of IFN-γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop. Exp Ther Med. 2021;21(2):112. https://doi.org/10.3892/etm.2020.9544.

Article  CAS  PubMed  Google Scholar 

Zhang L, Qu YN, Zhang HY, Wu ZY, Li ZL, Guo WB, et al. SOCS1 regulates the immunomodulatory roles of MSCs on B cells. Int J Stem Cells. 2020;13(2):237–45. https://doi.org/10.15283/ijsc20001.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qiu LJ, Xu K, Liang Y, Cen H, Zhang M, Wen PF, et al. Decreased SOCS1 mRNA expression levels in peripheral blood mononuclear cells from patients with systemic lupus erythematosus in a Chinese population. Clin Exp Med. 2015;15(3):261–7. https://doi.org/10.1007/s10238-014-0309-2.

Article  CAS  PubMed  Google Scholar 

Reily C, Rice T, Crossman DK, Rizk DV. Phosphatase control of cytokine-mediated overproduction of galactose-deficient IgA1, the main autoantigen in IgA nephropathy. J Autoimmun. 2022;132:102883. https://doi.org/10.1016/j.jaut.2022.102883.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461. https://doi.org/10.3389/fimmu.2014.00461.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Çakan E, Ah Kioon MD, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, et al. TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance. J Exp Med. 2023;220(12). https://doi.org/10.1084/jem.20230944.

Zhang S, Cao X. TLR9 triggers MyD88-independent anti-inflammatory signaling in lupus. Trends Immunol. 2023;44(3):153–5. https://doi.org/10.1016/j.it.2023.01.008.

Article  CAS  PubMed  Google Scholar 

Zhang J, Mi Y, Zhou R, Liu Z, Huang B, Guo R, et al. The TLR4-MyD88-NF-κB pathway is involved in sIgA-mediated IgA nephropathy. J Nephrol. 2020;33(6):1251–61. https://doi.org/10.1007/s40620-020-00722-3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suzuki H, Suzuki Y, Narita I, Aizawa M, Kihara M, Yamanaka T, et al. Toll-like receptor 9 affects severity of IgA nephropathy. J Am Soc Nephrol. 2008;19(12):2384–95. https://doi.org/10.1681/asn.2007121311.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Makita Y, Suzuki H, Kano T, Takahata A, Julian BA, Novak J, et al. TLR9 activation induces aberrant IgA glycosylation via APRIL- and IL-6-mediated pathways in IgA nephropathy. Kidney Int. 2020;97(2):340–9. https://doi.org/10.1016/j.kint.2019.08.022.

Article  CAS  PubMed  Google Scholar 

Liu C, Ye MY, Yan WZ, Peng XF, He LY, Peng YM. MicroRNA-630 regulates underglycosylated IgA1 production in the tonsils by targeting TLR4 in IgA nephropathy. Front Immunol. 2020;11:563699. https://doi.org/10.3389/fimmu.2020.563699.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu C, Li X, Shuai L, Dang X, Peng F, Zhao M, et al. Astragaloside IV inhibits galactose-deficient IgA1 secretion via miR-98-5p in pediatric IgA nephropathy. Front Pharmacol. 2021;12:658236. https://doi.org/10.3389/fphar.2021.658236.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Novak J, Tomana M, Matousovic K, Brown R, Hall S, Novak L, et al. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int. 2005;67(2):504–13. https://doi.org/10.1111/j.1523-1755.2005.67107.x.

Article  CAS  PubMed  Google Scholar 

Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22(10):1795–803. https://doi.org/10.1681/asn.2011050464.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Serino G, Sallustio F, Cox SN, Pesce F, Schena FP. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 2012;23(5):814–24. https://doi.org/10.1681/asn.2011060567.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clough E, Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, et al. NCBI GEO: archive for gene expression and epigenomics data sets: 23-year update. Nucleic Acids Res. 2024;52(D1):D138–44. https://doi.org/10.1093/nar/gkad965.

Article  CAS  PubMed  Google Scholar 

Yang WG, Sun A, Zhu R, Liu N, He WJ, Liu LL. Exploration of artemisinin against IgA nephropathy via AKT/Nrf2 pathway by bioinformatics and experimental validation. Drug Des Dev Ther. 2023;17:1679–97. https://doi.org/10.2147/dddt.s403422.

Article  CAS 

Comments (0)

No login
gif