Macrophage Zc3h12c Limits Tissue Inflammation and Injury via Alternative Splicing of Pre‐mRNA
Source abstract
Abstract
Abstract RNA‐binding proteins regulate post‐transcriptional gene translation, but the macrophage‐specific role of Zc3h12c remains poorly characterized. Here, the role of Zc3h12c in macrophages is characterized using Tnfrsf11a Cre ‐Zc3h12c flox/flox mice. Both Tnfrsf11a and Zc3h12c are highly expressed in the kidney tissue from patients with chronic kidney disease and showed a positive association with an interstitial fibrosis score. Single cell RNA sequencing demonstrated abundant Tnfrsf11a expression in murine kidney macrophages and a correlation with the induction of chemokines, macrophage phagocytosis, and activation upon kidney injury. In various kidney injury models, Tnfrsf11a Cre ‐Zc3h12c flox/flox mice suffered from more injury and inflammation in the kidney, characterized by an increase in Ccr2 positive leukocyte infiltration. Mechanistic in vitro studies revealed that Zc3h12c suppresses macrophage activation toward a pro‐inflammatory phenotype, modulates macrophage survival, migration, and phagocytosis. Both in silico and in vitro analysis indicated that Zc3h12c regulates the pro‐inflammatory cytokines/chemokines and chemokine receptors expression and modulates the alternative splicing of pre‐mRNAs STAT1. Thus, macrophage‐derived Zc3h12c limits tissue inflammation and injury, potentially via alternate splicing of pre‐mRNAs.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: RNA Research and Splicing · MicroRNA in disease regulation · RNA regulation and disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Division of Nephrology Department of Medicine IV Hospital of the Ludwig‐Maximilians University 80336 Munich Germany
Department of Nephrology The Affiliated Hospital of Qingdao University Qingdao 266005 China
Department of Pharmacy Ludwig‐Maximilians‐Universität München 81377 Munich Germany
Department of Rheumatology Endocrinology and Nephrology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo 060‐8638 Japan
Department of Nephrology Shanxi Provincial People's Hospital The Fifth Clinical Medical College of Shanxi Medical University Taiyuan Shanxi 030012 China
Renal Electrolyte and Hypertension Division Department of Medicine University of Pennsylvania Perelman School of Medicine Philadelphia 19104 USA
Institute for Diabetes Obesity and Metabolism University of Pennsylvania Perelman School of Medicine Philadelphia 19104 USA
Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia 19104 USA
Department of Cardiology Klinikum der Universität München Ludwig‐Maximilians‐Universität 81377 Munich Germany
DZHK (German Centre for Cardiovascular Research) partner site Munich Heart Alliance 80636 Munich Germany
Department of Immunopharmacology Mannheim Institute for Innate Immunoscience (MI3) Medical Faculty Mannheim Heidelberg University 68167 Mannheim Germany
Funding
Deutsche Forschungsgemeinschaft · H2020 European Research Council · National Institutes of Health
References (95)
Show source-provided references
1. 10.1016/j.cell.2022.10.00710.1016/j.cell.2022.10.007 ↗
2. 10.1016/j.bbadis.2012.12.00110.1016/j.bbadis.2012.12.001 ↗
3. 10.1038/nrneph.2017.210.1038/nrneph.2017.2 ↗
4. 10.1681/ASN.200906061510.1681/ASN.2009060615 ↗
5. 10.1073/pnas.091222810710.1073/pnas.0912228107 ↗
6. 10.1038/nrneph.2014.6810.1038/nrneph.2014.68 ↗
7. 10.2353/ajpath.2008.07072610.2353/ajpath.2008.070726 ↗
8. 10.1146/annurev-immunol-061020-05373410.1146/annurev-immunol-061020-053734 ↗
9. 10.1126/science.aau096410.1126/science.aau0964 ↗
10. 10.1146/annurev-immunol-101819-07514710.1146/annurev-immunol-101819-075147 ↗
11. 10.1038/nature0792410.1038/nature07924 ↗
12. 10.1084/jem.2018176210.1084/jem.20181762 ↗
13. 10.1016/j.omto.2021.02.00510.1016/j.omto.2021.02.005 ↗
14. 10.1016/j.cellsig.2011.10.01110.1016/j.cellsig.2011.10.011 ↗
15. 10.1080/15476286.2020.179558410.1080/15476286.2020.1795584 ↗
16. 10.1101/sqb.2013.78.01987710.1101/sqb.2013.78.019877 ↗
17. 10.1016/j.bbamcr.2012.06.02910.1016/j.bbamcr.2012.06.029 ↗
18. 10.1074/jbc.M70786120010.1074/jbc.M707861200 ↗
19. 10.1038/ni.213710.1038/ni.2137 ↗
20. 10.1261/rna.071381.11910.1261/rna.071381.119 ↗
21. 10.1042/BJ2013001910.1042/BJ20130019 ↗
22. 10.1016/j.cellimm.2024.10483710.1016/j.cellimm.2024.104837 ↗
23. 10.1038/s41467-021-24352-w10.1038/s41467-021-24352-w ↗
24. 10.1038/s41467-019-09028-w10.1038/s41467-019-09028-w ↗
25. 10.1016/j.kint.2022.11.01210.1016/j.kint.2022.11.012 ↗
26. 10.1016/j.bbadis.2021.16608610.1016/j.bbadis.2021.166086 ↗
27. 10.3389/fimmu.2021.62792210.3389/fimmu.2021.627922 ↗
28. 10.1242/dmm.04758910.1242/dmm.047589 ↗
29. 10.1159/00044803810.1159/000448038 ↗
30. 10.1111/imcb.1252110.1111/imcb.12521 ↗
31. 10.1016/j.jim.2014.05.00910.1016/j.jim.2014.05.009 ↗
32. 10.1038/1685210.1038/16852 ↗
33. 10.1172/JCI3680910.1172/JCI36809 ↗
34. 10.1038/s41586-018-0482-710.1038/s41586-018-0482-7 ↗
35. 10.1038/s41467-020-18287-x10.1038/s41467-020-18287-x ↗
36. 10.1038/s41467-018-07685-x10.1038/s41467-018-07685-x ↗
37. 10.1038/cddis.2017.50510.1038/cddis.2017.505 ↗
38. 10.1002/jbmr.49010.1002/jbmr.490 ↗
39. 10.1126/science.aaf423810.1126/science.aaf4238 ↗
40. 10.1016/j.jim.2016.04.00410.1016/j.jim.2016.04.004 ↗
41. 10.1023/A:100894282896010.1023/A:1008942828960 ↗
42. 10.1038/nm.265310.1038/nm.2653 ↗
43. 10.1371/journal.pone.014948910.1371/journal.pone.0149489 ↗
44. 10.1152/ajprenal.00488.201510.1152/ajprenal.00488.2015 ↗
45. 10.14814/phy2.1322810.14814/phy2.13228 ↗
46. 10.1371/journal.pbio.100041210.1371/journal.pbio.1000412 ↗
47. 10.1371/journal.pbio.300041010.1371/journal.pbio.3000410 ↗
48. 10.1002/advs.20210367510.1002/advs.202103675 ↗
49. 10.1172/jci.insight.16107810.1172/jci.insight.161078 ↗
50. 10.1038/s41586-023-05769-310.1038/s41586-023-05769-3 ↗
51. 10.1186/s13059-017-1382-010.1186/s13059-017-1382-0 ↗
52. Lun A. T. · F1000Res · 2016 · 5 · 2122
53. 10.1038/s41592-019-0619-010.1038/s41592-019-0619-0 ↗
54. 10.1038/nbt.319210.1038/nbt.3192 ↗
55. 10.1038/s41587-019-0201-410.1038/s41587-019-0201-4 ↗
56. 10.1093/bioinformatics/btp35210.1093/bioinformatics/btp352 ↗
57. 10.1093/bioinformatics/btt65610.1093/bioinformatics/btt656 ↗
58. 10.1038/nbt.326910.1038/nbt.3269 ↗
59. 10.1089/omi.2011.011810.1089/omi.2011.0118 ↗
60. 10.1038/s43018-022-00356-310.1038/s43018-022-00356-3 ↗
61. 10.1126/science.aax919810.1126/science.aax9198 ↗
62. Karlsson M. · Sci. Adv. · 2021 · 7 · 31
63. 10.1172/JCI7212610.1172/JCI72126 ↗
64. 10.1101/gr.258848.11910.1101/gr.258848.119 ↗
65. 10.1038/nrm164510.1038/nrm1645 ↗
66. 10.1186/gb-2014-15-1-r2610.1186/gb-2014-15-1-r26 ↗
67. 10.3390/genes1410189610.3390/genes14101896 ↗
68. 10.1093/nar/gky40110.1093/nar/gky401 ↗
69. 10.1038/ncomms1084610.1038/ncomms10846 ↗
70. 10.1016/j.celrep.2019.09.07810.1016/j.celrep.2019.09.078 ↗
71. 10.1016/j.jmb.2024.16849710.1016/j.jmb.2024.168497 ↗
72. 10.1128/JVI.01359-1010.1128/JVI.01359-10 ↗
73. 10.1186/s41232-019-0111-310.1186/s41232-019-0111-3 ↗
74. 10.11005/jbm.2023.30.2.12710.11005/jbm.2023.30.2.127 ↗
75. 10.1084/jem.190.12.174110.1084/jem.190.12.1741 ↗
76. 10.1186/s12882-024-03648-110.1186/s12882-024-03648-1 ↗
77. 10.1016/j.trim.2020.10126310.1016/j.trim.2020.101263 ↗
78. 10.1155/2016/140592410.1155/2016/1405924 ↗
79. 10.1371/journal.pone.004133110.1371/journal.pone.0041331 ↗
80. 10.1161/01.RES.0000220106.64661.7110.1161/01.RES.0000220106.64661.71 ↗
81. 10.1007/s00395-015-0483-810.1007/s00395-015-0483-8 ↗
82. 10.1016/j.cell.2015.04.02910.1016/j.cell.2015.04.029 ↗
83. 10.1038/cmi.2016.7010.1038/cmi.2016.70 ↗
84. 10.1186/1742-2094-8-18210.1186/1742-2094-8-182 ↗
85. Jin Z. · J. Neuroinflammation · 2013 · 10 · 63
86. 10.3390/ijms2013321410.3390/ijms20133214 ↗
87. 10.26508/lsa.20240278410.26508/lsa.202402784 ↗
88. 10.1016/j.bbalip.2019.06.00610.1016/j.bbalip.2019.06.006 ↗
89. 10.1016/j.molimm.2020.10.02310.1016/j.molimm.2020.10.023 ↗
90. 10.1038/cddis.2017.48110.1038/cddis.2017.481 ↗
91. 10.1016/j.fsi.2019.01.03710.1016/j.fsi.2019.01.037 ↗
92. 10.1126/science.819745510.1126/science.8197455 ↗
93. 10.1038/s41392-021-00791-110.1038/s41392-021-00791-1 ↗
94. 10.1128/JVI.00344-0810.1128/JVI.00344-08 ↗
95. 10.1016/j.virol.2010.02.02310.1016/j.virol.2010.02.023 ↗