Effects of the tumor suppressor PTEN on biological behaviors of activated pancreatic stellate cells in pancreatic fibrosis

• Published in: Experimental cell research 2018-12, Vol.373 (1-2), p.132-144
• Main Authors: Zhang, Xiaoyun, Jin, Tong, Huang, Xiaoxi, Liu, Xinjuan, Liu, Zheng, Jia, Yanjun, Hao, Jianyu
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; APOPTOSIS; COLLAGEN; Extracellular matrix; PANCREAS; Pancreatic fibrosis; Pancreatic stellate cells; PHOSPHATASES; PTEN; RATS; α-smooth muscle actin
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2018.10.005

Pancreatic stellate cells (PSCs), when activated, are characterized by proliferation and collagen synthesis, and contribute to extracellular matrix deposition in pancreatic fibrosis. Concomitantly, fibrosis is linked with the loss of PTEN (phosphatase and tensin homolog) protein in several organs. This study investigated the association between PTEN protein levels and the activated or apoptotic status of PSCs in a rat model of chronic pancreatitis. In addition, the activation status and biological behaviors of culture-activated PSCs were analyzed after lentiviral transfection with wildtype or mutant (G129E) PTEN for upregulation, or PTEN short hairpin RNA for downregulation, of PTEN. In vivo, PTEN levels gradually decreased during pancreatic fibrosis, which positively correlated with apoptosis of activated PSCs, but negatively with PSC activation. In vitro, activated PSCs with wildtype PTEN showed less proliferation, migration, and collagen synthesis compared with control PSCs, and greater numbers were apoptotic; activated PSCs with mutant PTEN showed similar, but weaker, effects. Furthermore, AKT and FAK/ERK signaling was involved in this process. In summary, activated PSCs during pancreatic fibrosis in vivo have lower levels of PTEN. In vitro, PTEN appears to prevent PSCs from further activation and promotes apoptosis through regulation of the AKT and FAK/ERK pathways. [Display omitted] •The PTEN level decreased in DBTC-induced pancreatic fibrosis.•PTEN expression correlates with the activation and apoptosis of PSCs in vivo.•PTEN modulation of activated PSCs involves the AKT and FAK/ERK pathways.•WT PTEN affects anti-fibrotic activity by regulating PSC behaviors in vitro.