• Yun Zheng, Jun Cheng, AFang Zhang, YuYang Wang, ChengCai Dai, and JiaBin Li.
• Department of Emergency ICU, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Anhui, Hefei, Shushan District, 230031, China.
• Injury. 2022 Feb 1; 53 (2): 416-421.

BackgroundMiR-29a targets signal transducers and activators of transcription 3 (STAT3) and negatively regulates its expression. Both miR-29a and STAT3 have been implicated in sepsis and upregulated miR-29a was associated with sepsis. However, the regulation of miR-29a in sepsis is not well elucidated.MethodsWe treated TC-1 cells with interleukin (IL)-6 and the expression of miR-29a and STAT3 was measured. We pre-treated TC-1 cells with histone deacetylase inhibitor Trichostatin A, DNA methylation inhibitor 5-Azacytidine or histone acetyltransferase inhibitor A-485, then treated cells with IL-6 and analyzed the expression of miR-29a and STAT3. We measured the expression of histone deacetylases and histone acetyltransferase, and glycolysis in IL-6-treated TC-1 cells. We administrated miR-29a inhibitor or STAT3 inhibitor to septic mice and the survival rate and expression of anti-apoptotic factors were measured.ResutlsIL-6 promoted miR-29a expression while suppressed STAT3 expression. Upregulation of miR-29a was associated with sepsis. Histone acetylation promoted miR-29a expression. IL-6 promoted glycolysis in TC-1 cells, which resulted in Acetyl-CoA accumulation. Inhibition of miR-29a promoted survival rate in septic mice while inhibiting STAT3 exacerbated death in mice. The protection of miR-29a inhibition against sepsis was abolished when STAT3 was inhibited.ConclusionHistone acetylation promoted miR-29a expression, resulting in downregulation of STAT3 and exacerbation of sepsis.Copyright © 2021. Published by Elsevier Ltd.

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