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).