Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target

Table 1

Biological and chemical factors inducing autophagy in gastric mucosa.

Factors	Agent	Effect	Mechanism	Reference
H. pylori (acute infection)	VacA	Reduces the stability of VacA, and limits toxin-induced cellular damage	Promotes autophagy in a VacA-dependent manner	[22]
	VacA	Induces apoptosis	Promotes autophagy by VacA receptor LRP1	[23]
	VacA	Induces apoptosis	Induces autophagic cell death via the endoplasmic reticulum stress pathway	[24]
	VacA	Induces apoptosis	Accumulates connexin 43 in autophagy vesicles via a Rac1/ERK dependent pathway	[25]
	CagA	Promotes the development of gastric cancer	Promotes the accumulation of CagA through VacA-mediated autophagy destruction	[26]
	CagA	Promotes inflammation	Decreases autophagy via c-met-PI3K/Akt-mTOR signaling pathway	[27]
	HP0175	Induces apoptosis	Promotes autophagy by HP0175, link UPR	[28]
	—	Promotes the development of gastric cancer.	Induces degradation of p14ARF and downregulates autophagy	[29]
	VacA	Induces lysosomal damage	Promotes autophagy by galectin-8 aggregation	[30]
	VacA	Promotes the survival and colonization of H. pylori	Destroys the activity of TRPML1 and inhibits lysosome and autophagy killing	[31]
	CagA	Promotes the development of gastric cancer	Inhibits CagA-degraded autophagy and CAPZA1 negatively regulates the formation of autolysomes by inhibiting the expression of LAMP1	[32]
	—	Promotes the survival and colonization of H. pylori	Inhibits lysosomal clearance of autophagosomes	[33]
H. pylori (chronic infection)	VacA (prolonged exposure)	Promotes inflammation and the development of gastric cancer	Decreases autophagy and accumulates defective autophagosomes due to lack of cathepsin D	[34]
Mir-30b		Promotes the survival and colonization of H. pylori	Inhibits autophagy by targeting ATG12 and BECN1	[35]
Mir-30d		Promotes the survival and colonization of H. pylori	Inhibits autophagy pathway	[36]
Mir-155		Decreases the survival of intracellular H. pylori	Promotes autophagy	[37]
	—	Induces inflammation	Promotes autophagy by upregulating STAT3 phosphorylation on Ser727	[38]
H. pylori lysate		Promotes the survival and colonization of H. pylori and the development of gastric cancer	Inhibits apoptosis and autophagy through the Nod1-NF-κB/MAPKERK/FOXO4 signaling pathway.	[39]
Ethanol		Induces gastric mucosal injury and active autophagy	Promotes autophagy by downregulating the mTOR signal pathway	[40]
Ochratoxin A		Induces apoptosis	Promotes autophagy by the AMPK/mTOR pathway	[41]
EV71		Induces inflammation	Increases autophagy, promotes the expression, and releases IL-6 by the P38MAPK/ERK pathway.	[42]
Sulindac sulfide		Induces apoptosis	Induces autophagic death via survivin downregulation	[43]
Aspirin		Induces gastrointestinal damage and apoptosis	Inhibits autophagy by activating mTOR-mediated ULK1 phosphorylation	[44]
EFL1		Induces apoptosis	Promotes autophagy by the PI3K/AKT/mTOR pathway	[45]