Hippo Pathway Activation in Aged Mesenchymal Stem Cells Contributes to the Dysregulation of Hepatic Inflammation in Aged Mice
Source abstract
Abstract
Abstract Aging is always accompanied by chronic diseases which probably attribute to long‐term chronic inflammation in the aging body. Whereas, the mechanism of chronic inflammation in aging body is still obscure. Mesenchymal stem cells (MSCs) are capable of local chemotaxis to sites of inflammation and play a powerful role in immune regulation. Whether degeneration of MSCs in the aging body is associated with unbalanced inflammation is still not clear. In this study, immunosuppressive properties of aged MSCs are found to be repressed. The impaired immunosuppressive function of aged MSCs is associated with lower expression of the Hippo effector Yes‐associated protein 1 (YAP1) and its target gene signal transducer and activator of transcription 1 (STAT1). YAP1 regulates the transcription of STAT1 through binding with its promoter. In conclusion, a novel YAP1/STAT1 axis maintaining immunosuppressive function of MSCs is revealed and impairment of this signal pathway in aged MSCs probably resulted in higher inflammation in aged mice liver.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Hippo pathway signaling and YAP/TAZ · Phagocytosis and Immune Regulation · Inflammasome and immune disorders
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
The Third Affiliated Hospital of Soochow University Institutes for Translational Medicine State Key Laboratory of Radiation Medicine and Protection Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province Medical College of Soochow University Soochow University Suzhou 215000 China
Department of Experimental Medicine TOR University of Rome Tor Vergata Rome 00133 Italy
Department of Tumor Immunology and Gene Therapy Center Third Affiliated Hospital of Naval Medical University Shanghai 200438 China
Department of immunology and metabolism National Center for Liver Cancer Shanghai 201805 China
Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences Xi'an Jiaotong University Xi'an Shaanxi 710061 China
Department of Clinical Pharmacology The Second Hospital of Anhui Medical University Hefei 230601 China
Department of Oncology The First Affiliated Hospital of Anhui Medical University Hefei Anhui 230022 China
Funding
National Natural Science Foundation of China · Shanghai Municipal Health Bureau
References (91)
Show source-provided references
1. 10.2337/diacare.27.3.81310.2337/diacare.27.3.813 ↗
2. 10.1016/j.neubiorev.2011.10.00110.1016/j.neubiorev.2011.10.001 ↗
3. 10.1016/j.jacc.2009.09.00910.1016/j.jacc.2009.09.009 ↗
4. 10.1002/med.101010.1002/med.1010 ↗
5. 10.1210/jc.2002-02151110.1210/jc.2002-021511 ↗
6. 10.1210/er.21.2.11510.1210/er.21.2.115 ↗
7. 10.1093/gerona/gls18710.1093/gerona/gls187 ↗
8. 10.1016/j.mad.2006.11.01610.1016/j.mad.2006.11.016 ↗
9. 10.1016/j.exger.2017.12.01510.1016/j.exger.2017.12.015 ↗
10. 10.1038/leu.2014.10810.1038/leu.2014.108 ↗
11. 10.1093/gerona/glw24010.1093/gerona/glw240 ↗
12. 10.1016/j.bpg.2009.10.00510.1016/j.bpg.2009.10.005 ↗
13. 10.1016/j.jhep.2010.06.00910.1016/j.jhep.2010.06.009 ↗
14. 10.1016/j.arr.2019.02.00210.1016/j.arr.2019.02.002 ↗
15. 10.21873/invivo.1161810.21873/invivo.11618 ↗
16. 10.1016/j.biocel.2003.11.00110.1016/j.biocel.2003.11.001 ↗
17. 10.1002/sctm.17-005110.1002/sctm.17-0051 ↗
18. 10.1182/blood-2004-04-148810.1182/blood-2004-04-1488 ↗
19. 10.3892/ijmm.2017.291210.3892/ijmm.2017.2912 ↗
20. 10.1186/s13578-020-00480-610.1186/s13578-020-00480-6 ↗
21. 10.1016/j.gene.2018.12.06310.1016/j.gene.2018.12.063 ↗
22. 10.1186/1479-5876-12-810.1186/1479-5876-12-8 ↗
23. 10.1111/j.1474-9726.2008.00377.x10.1111/j.1474-9726.2008.00377.x ↗
24. 10.3390/cells805039810.3390/cells8050398 ↗
25. 10.1038/s41423-018-0007-110.1038/s41423-018-0007-1 ↗
26. 10.1016/j.phrs.2019.03.01810.1016/j.phrs.2019.03.018 ↗
27. 10.1016/j.devcel.2010.09.01110.1016/j.devcel.2010.09.011 ↗
28. 10.1016/j.ceb.2016.08.00410.1016/j.ceb.2016.08.004 ↗
29. 10.1016/j.cell.2015.10.04410.1016/j.cell.2015.10.044 ↗
30. 10.1038/nrm222110.1038/nrm2221 ↗
31. 10.1101/gad.296640.11710.1101/gad.296640.117 ↗
32. 10.1371/journal.pbio.300059110.1371/journal.pbio.3000591 ↗
33. 10.1016/j.cell.2015.12.02910.1016/j.cell.2015.12.029 ↗
34. 10.1172/JCI8875910.1172/JCI88759 ↗
35. 10.1038/icb.2011.5910.1038/icb.2011.59 ↗
36. 10.1016/j.intimp.2021.10838010.1016/j.intimp.2021.108380 ↗
37. 10.1515/biol-2022-001310.1515/biol-2022-0013 ↗
38. 10.1177/002367721557284110.1177/0023677215572841 ↗
39. 10.1172/JCI9083010.1172/JCI90830 ↗
40. 10.1053/gast.1996.v111.pm869021310.1053/gast.1996.v111.pm8690213 ↗
41. Ballegeer M. · J. Gastroenterol. Hepatol. Res. · 2016 · 1
42. 10.1016/j.stem.2014.06.00810.1016/j.stem.2014.06.008 ↗
43. 10.1038/s42003-021-02175-110.1038/s42003-021-02175-1 ↗
44. 10.1038/s41467-019-11100-410.1038/s41467-019-11100-4 ↗
45. 10.1038/ncb353010.1038/ncb3530 ↗
46. 10.1111/j.1582-4934.2009.00912.x10.1111/j.1582-4934.2009.00912.x ↗
47. 10.1038/nm.197910.1038/nm.1979 ↗
48. 10.1038/srep1776210.1038/srep17762 ↗
49. 10.1016/j.stem.2007.11.01410.1016/j.stem.2007.11.014 ↗
50. 10.1038/nm.356210.1038/nm.3562 ↗
51. 10.4161/23723548.2014.97005510.4161/23723548.2014.970055 ↗
52. 10.1016/j.stem.2014.07.00110.1016/j.stem.2014.07.001 ↗
53. 10.1038/cdd.2014.8510.1038/cdd.2014.85 ↗
54. 10.1016/j.ejphar.2004.07.03010.1016/j.ejphar.2004.07.030 ↗
55. 10.5483/BMBRep.2018.51.3.01510.5483/BMBRep.2018.51.3.015 ↗
56. 10.1038/onc.2017.2410.1038/onc.2017.24 ↗
57. 10.1101/gad.166440810.1101/gad.1664408 ↗
58. 10.1016/j.stem.2019.02.01810.1016/j.stem.2019.02.018 ↗
59. 10.1038/nature0926210.1038/nature09262 ↗
60. Xie L. · Stem Cells Int. · 2015
61. 10.1016/j.joca.2019.04.00210.1016/j.joca.2019.04.002 ↗
62. 10.1016/j.gpb.2022.01.00510.1016/j.gpb.2022.01.005 ↗
63. 10.1186/s12917-021-03100-810.1186/s12917-021-03100-8 ↗
64. 10.1038/nm.196410.1038/nm.1964 ↗
65. 10.1016/S0002-9440(10)63950-810.1016/S0002-9440(10)63950-8 ↗
66. 10.1002/eji.20042513910.1002/eji.200425139 ↗
67. 10.1038/cdd.2009.16510.1038/cdd.2009.165 ↗
68. 10.1016/S0168-8278(96)80301-110.1016/S0168-8278(96)80301-1 ↗
69. 10.3748/wjg.v18.i2.11910.3748/wjg.v18.i2.119 ↗
70. 10.1002/hep.2044710.1002/hep.20447 ↗
71. 10.4049/jimmunol.172.1.4510.4049/jimmunol.172.1.45 ↗
72. 10.1038/286725a010.1038/286725a0 ↗
73. 10.1371/journal.pbio.300020110.1371/journal.pbio.3000201 ↗
74. 10.15252/emmm.20150608910.15252/emmm.201506089 ↗
75. 10.1016/j.ejps.2016.10.00210.1016/j.ejps.2016.10.002 ↗
76. 10.1016/j.mad.2020.11128010.1016/j.mad.2020.111280 ↗
77. 10.1158/0008-5472.CAN-20-050610.1158/0008-5472.CAN-20-0506 ↗
78. 10.4161/cam.2063110.4161/cam.20631 ↗
79. 10.4161/cc.2232210.4161/cc.22322 ↗
80. 10.1016/j.pharmthera.2010.10.00710.1016/j.pharmthera.2010.10.007 ↗
81. 10.1038/nrd.2017.17810.1038/nrd.2017.178 ↗
82. 10.1016/j.csbj.2019.08.00510.1016/j.csbj.2019.08.005 ↗
83. 10.1016/j.jbc.2022.10177910.1016/j.jbc.2022.101779 ↗
84. 10.1038/nrd416110.1038/nrd4161 ↗
85. Stuart T. · Compr. Integr. Single‐Cell Data Cell · 2019 · 177 · 1888
86. 10.1038/s41590-018-0276-y10.1038/s41590-018-0276-y ↗
87. 10.1136/jitc-2021-00280910.1136/jitc-2021-002809 ↗
88. Wang H. · Mol. Med. Rep. · 2019 · 20 · 488310.3892/mmr.2019.10388 ↗
89. 10.1007/978-1-4939-2815-6_110.1007/978-1-4939-2815-6_1 ↗
90. 10.1038/nprot.2009.23810.1038/nprot.2009.238 ↗
91. 10.1186/1741-7015-10-9810.1186/1741-7015-10-98 ↗