3.6 Necroptosis in other fibrosis
Duchenne muscular dystrophy (DMD), a severe degenerative disease triggered by dystrophin gene mutations,is traited with progressive myofibre necrosis. Researchers found that RIPK1, RIPK3 and MLKL are increased in dystrophic mouse myofibres which indicated that necroptosis maybe the potential mechanism of myofibre death in DMD (Morgan et al. 2018). Atherosclerosis is a lipoprotein-driven disease that results in plaque formation at particular locations of the arterial tree through intimal inflammation, fibrosis, and calcification (Bentzon et al. 2014). RIPK3 and MLKL are increased in humans with unstable carotid atherosclerosis, meanwhile, phosphorylated MLKL is detected in advanced atheromas. Inhibition of macrophage necroptosis by Nec-1 can reduce lesion size of atherosclerotic plaques in Apoe (-/-) mice (Karunakaran et al. 2016). Targeting necroptosis may be effective strategies for novel drug discovery for atherosclerosis (Coornaert et al. 2018). Long term inflammatory bowel diseases (IBD) can trigger intestinal fibrosis (Rieder, Fiocchi and Rogler 2017). Previous literature reported that RIPK3, MLKL were up-regulation in children with IBD, which indicated that necroptosis is closely related with intestinal inflammation in children with IBD and contributes to strengthen the inflammatory process. Therefore, researchers speculate that RIP3 and MLKL can be the represent powerful targets for the treatment of human IBD (Pierdomenico et al. 2014).