The Link between Circadian Clock Genes and Autophagy in Chronic Obstructive Pulmonary Disease

Figure 2

Circadian rhythm and autophagy regulation in COPD. The conversion of LC3-I to LC3-II is regarded as an indicator of autophagosome formation [47]. Meanwhile, autophagy proteins BECLIN 1 and ATG5-ATG12 are also involved in the formation of autophagosomes [48]. Autophagosome and lysosome form autolysosome under the digestion of lysosomal hydrolase [49]. CS exposure breaks the balance of the autophagy level and promotes COPD progression by enhancing inflammation and oxidative stress. The core clock protein Per2 can activate autophagy by specifically inhibiting the activity of mTORC1. mTOR in the macromolecular complex (mTOR complex 1 [(mTORC1)) negatively regulates autophagy and activates melatonin, while melatonin inhibits the NLRP3 inflammasome and IL-1β to alleviate airway inflammation. C/EBPβ is involved in COPD development by participating in the expression of the inflammatory mediator CXCL1 in HBECs and the aggregation of neutrophils. CS exposure increases the expression of p62, inducing aggregation of ubiquitinated proteins and the TFEB in aggresome-bodies while participate in autophagy by regulating core clock genes. p62: the autophagy impairment marker; TFEB: autophagy transcription factor; REV-ERBα (Nr1d1): an important component in core circadian clock molecules; Ub-p, ubiquitinated protein.