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.

在慢性胰腺炎中，PSC 被促炎细胞因子激活以诱导胰腺纤维化。HDAC 抑制通过诱导细胞凋亡和抑制炎症来防止胰腺纤维化和 PSC 细胞凋亡。在我们的研究中，我们发现 miR-15 和 miR-16 在慢性胰腺炎中显着降低，HDAC 抑制可以恢复这两种 miRNA 的水平。HDAC 调节 miR-15 和 miR-16 的转录，进而调节 PSC 的凋亡和纤维化。并且我们证明了Bcl-2和Smad5是miR-15和miR-16的靶基因，这说明了HDAC抑制如何减轻慢性胰腺炎中PSCs的凋亡和纤维化。这些结果表明，HDAC 抑制通过促进细胞凋亡和 TGF-β/Smads 信号通路来防止 CP，