Mucosal healing and inflammatory bowel disease: Therapeutic implications and new targets

Table 2 Summary of molecular pathways involved in mucosal healing

Pathways/ Mechanism of action	Associated models studied	Ref.
EGFR signaling	In vitro, colorectal cancer mice, EGFR mutant mice	[43,116]
Hippo/YAP signaling	In vitro, YAP-1 transgenic mice	[36,59]
Notch signaling	Villin-Claudin-1 transgenic mice	[41,42]
Wnt/β-catenin signaling	In vitro and In vivo models of injury/repair	[44,60,61]
Vitamin D receptor (VDR) signaling	In vitro, VDR knockout mice	[45]
Src/focal adhesion kinase	In vitro, Mechanical colonic wound in mice, Nox1 and AnxA1 knockout mice, oral gavage in mice	[76-78]
Autophagy/ATG16L1	Patient biopsies; ATG16L1 T300A knock-in mice; Atg5-manipulated mice	[6,7,104]
SCFA-mediated signaling [acetate, propionate, butyrate, etc.]	In vitro, Patient biopsies, oral gavage in mice. T-cell induced colitis, trinitrobenzenesulphonic acid (TNBS) colitis	[83-85,91,93,100,101,114]
TLR-mediated signaling	DSS colitis	[109,110,112]
MyD88 mediated bacterial sensing	Mechanical colonic wound, MyD88 knockout mice	[111]
Prostaglandin-endoperoxidase synthase 2 enzyme (PGE2)	In vitro, mechanical colonic wound, Ptgs2 knockout mice, Ptger4 knockout mice	[111,112]
Mucin 2 signaling	In vitro, DSS colitis, EGFR mutant mice	[80,116]
IL-6/IL-22/IL-23/STAT3 signaling	DSS colitis, Th2-mediated colitis, cytokine deficient mice, bone marrow transplant mice, T-cell induced colitis, human and mouse intestinal organoid culture	[94,97,98,136-138]
TGF-β signaling	In vitro, DSS colitis, TGF-β transgenic mice	[50,130,131]
IL-10 signaling	In vitro, mechanical colonic wound in mice, IL-10-deficient mice	[132,133]

EGFR: Epidermal growth factor receptor; YAP: Yes-associated protein 1; ATG16L1: Autophagy related 16 like 1 protein; Atg5: Autophagy related 5; SCFA: Short chain fatty acid; TNBS: Trinitrobenzenesulphonic acid; TLR: Toll-like receptor; DSS: Dextran sodium sulfate; PGE2: Prostaglandin-endoperoxidase synthase 2 enzyme; IL: Interleukin; STAT3: Signal transducer and activator of transcription 3; TGF-β: Transforming growth factor-β.