3.5 Necroptosis in pancreatitis fibrosis
Acute pancreatitis (AP), characterized by acinar cell necroptosis and phlogosis responses, can progress into chronic pancreatitis accompanied with fibrosis. Recent study discovered that the main components of necroptosis , RIPK1 and RIPK3 exert dual function in AP. RIPK3 through phosphorylating MLKL promote acinar cell necroptosis, but RIPK1 maybe inhibit acinar cell necroptosis by activating the NF-κB signaling pathway in AP animal model (Wu et al. 2017). Another experiment found that RIP3 knockout can avoid tissue damage which induced by inflammation and further improve AP in an AP animal model (He et al. 2009, Zhang et al. 2009). Moreover, MLKL deficiency can improve the severity of cerulean-induced AP in mice (Wu et al. 2013). Chronic pancreatitis (CP) is defined as a pathological fibro-inflammatory syndrome which characterized by acinar cell injury and stress responses, duct dysfunction, persistent or altered inflammation (Kleeff et al. 2017). Pancreatic fibrosis is a significant characteristic of chronic pancreatitis, which contributes to sustaining and eternal injury in the pancreas. Pancreatic stellate cells serves as a primary source of ECM deposition in the period of pancreatic injury, and sustaining activation of pancreatic stellate cells plays an important part in the process of pancreatic fibrosis (Xue et al. 2015). Experiment with Atg7 deficiency Mice indicate that RIPK3, the core protein involved in necroptosis, can attenuates the chronic pancreatitis induced by deletion of ATG7 (Zhou et al. 2017). In short, current studies show that necroptosis plays an important role in acute and chronic pancreatitis and its fibrosis, the core proteins may be a potential target for clinical treatment of pancreatic diseases, but the specific mechanism remains to be further studied.