2. Academic Validation
  3. SPOP inhibits mice pancreatic stellate cell activation by promoting FADD degradation in cerulein-induced chronic pancreatitis

SPOP inhibits mice pancreatic stellate cell activation by promoting FADD degradation in cerulein-induced chronic pancreatitis

  • Exp Cell Res. 2019 Nov 1;384(1):111606. doi: 10.1016/j.yexcr.2019.111606.
Peng Tan 1,  Ankang Wang 2,  Hao Chen 2,  Yichao Du 1,  Baolin Qian 2,  Hao Shi 2,  Yajun Zhang 3,  Xianming Xia 1,  Wenguang Fu 4
Affiliations

Affiliations

  • 1 Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 2 Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 3 Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, Chongqing, 402160, China.
  • 4 Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, China. Electronic address: fuwenguang829@126.com.
PMID: 31493386 DOI: 10.1016/j.yexcr.2019.111606
Abstract

Pancreatic stellate cells (PSCs) have been recognized as key mediators of pancreatic fibrosis, a characteristic feature of chronic pancreatitis (CP). As a cullin-based E3 ubiquitin Ligase, speckle-type POZ protein (SPOP) has been identified to participate in tumorigenesis and organ development. However, its biological role in CP remains unknown. Therefore, this study sought to investigate the changed expression of SPOP in CP and to examine the effect on mice PSCs activation of SPOP. We found that SPOP was downregulated in the pancreatic tissues of cerulein-induced CP mice. siRNA-mediated knockdown of SPOP led to significant promotion in primary PSCs activity by activating the nuclear factor-kappaB (NF-κB)/interleukin-6 (IL-6) signaling pathway. In addition, we examined the effects of Fas-associated death domain (FADD), a proven SPOP substrate that activates NF-κB, on the regulation of PSCs activation. We found that FADD was downregulated by SPOP via interaction-mediated degradation, and was upregulated during PSCs activation. The promotion of PSCs activation in knocking down SPOP with siSPOP-1 were counteracted by knocking down FADD. The results suggest that the SPOP-induced inhibition of PSCs activation partially depended on FADD. These results highlight the importance of SPOP in CP and provide a potential target for therapeutic intervention.

Keywords

Cerulein; Chronic pancreatitis; FADD; Pancreatic stellate cells; SPOP.

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