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Aug 16, 2024;27 (8): 110483.

MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway.

Bingsi Tang, Jiangfan Yu, Rui Tang, Xinglan He, Jiani Liu, Licong Liu, Zehong Song, Yaqian Shi, Zhuotong Zeng, Yi Zhan, Xiangning Qiu, Yangfan Xiao, Yan Ding, Rong Xiao
Author Information
  1. Bingsi Tang: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  2. Jiangfan Yu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  3. Rui Tang: Department of Rheumatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  4. Xinglan He: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  5. Jiani Liu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  6. Licong Liu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  7. Zehong Song: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  8. Yaqian Shi: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  9. Zhuotong Zeng: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  10. Yi Zhan: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  11. Xiangning Qiu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  12. Yangfan Xiao: Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
  13. Yan Ding: Department of Dermatology, Hainan Provincial Hospital of Skin Disease, Haikou, Hainan 570100, China.
  14. Rong Xiao: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
PMID: 39156653 DOI: 10.1016/j.isci.2024.110483

Abstract

Systemic sclerosis (SSc) is an autoimmune disease affecting multiple tissues. The underlying causes and mechanisms of subcutaneous adipose tissue (SAT) loss in SSc remain unclear. Recent studies have highlighted the role of microRNAs in adipogenesis. Our study found that miR-4769-3p was upregulated in SSc patients and its silencing promoted SAT recovery in bleomycin-induced SSc mice, suggesting that miR-4769-3p might affect adipogenesis in SSc. Manipulating miR-4769-3p expression in 3T3-L1 cells revealed that its inhibition enhanced adipogenesis, while its overexpression weakened it. Further investigations showed that miR-4769-3p bound to 3'UTR of ubiquitin-specific protease-18 (USP18), inhibiting its expression, while USP18 interacted with voltage-dependent anion channel-2 (VDAC2), both of which were reduced in SSc. Silencing either USP18 or VDAC2 attenuated adipogenesis. Notably, USP18 inhibited VDAC2 ubiquitination and degradation, whereas miR-4769-3p reversed the VDAC2-induced elevation of adipogenesis, suggesting that miR-4769-3p inhibited adipogenesis by negatively regulating the USP18/VDAC2 pathway, providing a potential therapeutic target for SSc.

Keywords

Cell biology Molecular biology

References

  1. Trends Endocrinol Metab. 2016 Jan;27(1):1-10 [PMID: 26643658]
  2. Int J Mol Sci. 2022 May 17;23(10): [PMID: 35628433]
  3. Cancer Biol Med. 2022 Feb 19;19(9): [PMID: 35179324]
  4. Int J Mol Sci. 2020 Sep 17;21(18): [PMID: 32957626]
  5. J Invest Dermatol. 2019 May;139(5):1002-1009 [PMID: 30879642]
  6. Sci Rep. 2020 Aug 21;10(1):14084 [PMID: 32826933]
  7. J Cell Biochem. 2011 Oct;112(10):3002-14 [PMID: 21678470]
  8. Arthritis Res Ther. 2018 Jul 11;20(1):145 [PMID: 29996896]
  9. Genomics. 2022 Jul;114(4):110391 [PMID: 35644411]
  10. Mol Aspects Med. 2024 Apr;96:101252 [PMID: 38325132]
  11. Arthritis Rheumatol. 2022 May;74(5):871-881 [PMID: 34807516]
  12. Curr Opin Rheumatol. 2017 Nov;29(6):585-590 [PMID: 28800024]
  13. Nat Rev Rheumatol. 2017 Feb;13(2):71-72 [PMID: 28077865]
  14. J Investig Med. 2020 Mar;68(3):786-791 [PMID: 31874933]
  15. Adv Sci (Weinh). 2022 Feb;9(4):e2104759 [PMID: 34898027]
  16. FASEB J. 2023 Aug;37(8):e23076 [PMID: 37432650]
  17. J Cell Sci. 2022 Mar 1;135(5): [PMID: 35067718]
  18. Biochem Biophys Res Commun. 2022 Jul 5;612:126-133 [PMID: 35525196]
  19. J Mol Med (Berl). 2024 Apr;102(4):465-478 [PMID: 38386070]
  20. Autoimmun Rev. 2019 Nov;18(11):102396 [PMID: 31520794]
  21. Cell Physiol Biochem. 2018;50(1):15-27 [PMID: 30278433]
  22. J Biol Chem. 2015 Jan 30;290(5):2604-16 [PMID: 25505173]
  23. Exp Dermatol. 2013 Nov;22(11):769-71 [PMID: 24118261]
  24. Int Immunopharmacol. 2023 Mar;116:109764 [PMID: 36706594]
  25. Exp Dermatol. 2014 Sep;23(9):629-31 [PMID: 24841073]
  26. Int J Mol Sci. 2023 Jan 16;24(2): [PMID: 36675310]
  27. Nat Commun. 2021 Jul 28;12(1):4583 [PMID: 34321484]
  28. Int J Mol Sci. 2022 Sep 14;23(18): [PMID: 36142646]
  29. Arthritis Rheumatol. 2015 Apr;67(4):1062-73 [PMID: 25504959]
  30. Genes Dis. 2020 Mar 19;8(3):344-352 [PMID: 33997181]
  31. Int J Dermatol. 2021 Mar;60(3):376-383 [PMID: 33377189]
  32. Cells. 2022 Oct 24;11(21): [PMID: 36359742]
  33. Mol Cancer Res. 2021 Apr;19(4):667-677 [PMID: 33380466]
  34. Plast Reconstr Surg. 2023 Jan 1;151(1):97-107 [PMID: 36206077]
  35. Front Mol Biosci. 2021 Nov 17;8:631152 [PMID: 34869576]
  36. Biomedicines. 2021 Oct 14;9(10): [PMID: 34680587]
  37. Stem Cell Res Ther. 2022 Oct 9;13(1):499 [PMID: 36210466]
  38. BMC Pulm Med. 2022 Dec 16;22(1):479 [PMID: 36522766]
  39. J Clin Invest. 2019 Dec 2;129(12):5327-5342 [PMID: 31503545]
  40. J Cell Physiol. 2022 Jan;237(1):169-177 [PMID: 34608987]
  41. Mol Neurobiol. 2024 Feb 10;: [PMID: 38340205]
  42. Sci Rep. 2020 Oct 12;10(1):16751 [PMID: 33046783]
  43. Sci Rep. 2020 Dec 8;10(1):21482 [PMID: 33293557]
  44. Sci Rep. 2022 Nov 7;12(1):18932 [PMID: 36344812]
  45. Arthritis Res Ther. 2017 Jun 17;19(1):144 [PMID: 28623945]
  46. Front Immunol. 2022 Apr 08;13:856036 [PMID: 35464474]
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