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HYAL‐1‐induced autophagy facilitates pancreatic fistula for patients who underwent pancreaticoduodenectomy
Author(s) -
Li Le,
Tian FengYu,
Yuan Yue,
Zhang Tao,
Yang WenBo,
Kong Rui,
Wang Gang,
Chen Hua,
Chen HongZe,
Hu JiSheng,
Zhang GuangQuan,
Zhao ZhongJie,
Wang XinLong,
Li GuanQun,
Sun Bei
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901583r
Subject(s) - pancreatic fistula , pancreatic cancer , autophagy , medicine , acinar cell , ampk , pancreatic duct , stat3 , cancer research , gastroenterology , kinase , endocrinology , protein kinase a , oncology , pancreas , signal transduction , biology , cancer , apoptosis , microbiology and biotechnology , biochemistry
Abstract The main mechanism of hyaluronidase 1(HYAL‐1) in the development of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) was unknown. In this study, a comprehensive inventory of pre‐, intra‐, and postoperative clinical and biological data of two cohorts (62 pancreatic cancer [PCa] and 111 pancreatic ductal adenocarcinoma [PDAC]) which could induce POPF were retrospectively analyzed. Then, a total of 7644 genes correlated with HYAL‐1 was predicted in PDAC tissues and the enriched pathway, kinase targets and biological process of those correlated genes were evaluated. Finally, a mouse pancreatic fistula (PF) model was first built and in vitro studies were performed to investigate the effects of HYAL‐1 on PF progression. Our data indicated that preoperative serum HYAL‐1 level, pancreatic fibrosis score, and pancreatic duct size were valuable factors for detecting POPF of Grade B and C. The serum HYAL‐1 level of 2.07 mg/ml and pancreatic fibrosis score of 2.5 were proposed as the cutoff values for indicating POPF. The bioinformatic analysis and in vitro and in vivo studies demonstrated that HYAL‐1 facilitates pancreatic acinar cell autophagy via the dephosphorylation of adenosine 5‘‐monophosphate‐activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) signaling pathways, which exacerbate pancreatic secretion and inflammation. In summary, the preoperative serum HYAL‐1 was a significant predictor for POPF in patients who underwent PD. Tumor‐induced HYAL‐1 is one of core risk in accelerating PF and then promoting pancreatic secretion and acute inflammation response through the AMPK and STAT3‐induced autophagy.