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.