1. Academic Validation
  2. HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis

HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis

  • Hum Cell. 2020 Oct;33(4):1006-1016. doi: 10.1007/s13577-020-00387-x.
Ting Ji 1 Weiguang Feng 2 Xiangcheng Zhang 1 Kui Zang 1 Xingxing Zhu 1 Futai Shang 3
Affiliations

Affiliations

  • 1 Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China.
  • 2 Intensive Care Unit, Huai'an No 4 People's Hospital, 128 Yan'an East Road, Qingjiangpu District, Huai'an, 223002, Jiangsu, China.
  • 3 Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China. Shangft@126.com.
Abstract

In chronic pancreatitis, PSCs are activated by proinflammatory cytokines to induce pancreatic fibrogenesis. HDAC inhibition protected against the pancreatic fibrosis and the Apoptosis of PSCs through induced Apoptosis and depressed inflammation. In our study, we found that miR-15 and miR-16 decreased significantly in chronic pancreatitis and HDAC inhibition could recover the levels of these two miRNAs. HDAC regulated the transcription of miR-15 and miR-16, which then modulate the Apoptosis and fibrosis of PSCs. And we proved that Bcl-2 and SMAD5 were the target genes of miR-15 and miR-16, which illustrated how HDAC inhibition alleviated the Apoptosis and fibrogenesis of PSCs in chronic pancreatitis. These results suggested that HDAC inhibition protects against CP by promoting Apoptosis and TGF-β/Smads signaling pathways, and indicated that HDAC inhibition is a potential therapy to alleviate CP patients in clinic, and these need to be explored further.

Keywords

Apoptosis; Chronic pancreatitis; HDAC inhibition; miR-15/miR-16.

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