TABLE 2.

Targets and new therapeutic strategies for intestinal fibrosis.

	Targets	MoA	Therapeutics	Modality	Delivery system	References
Molecular level	Noncoding RNAs	Reduction of abnormal expression of colonic fibronectin collagen I protein	MiR‐200b	RNA	Microvesicles	29
	Signaling pathway	Inhibition of TGF‐β1 pathway	Vivomixx®	Multi‐strain probiotic	Capsule	36
		Inhibition of TGF‐β1 pathway	ACE‐I	Small‐molecule	PEG‐suspension	37
		Inhibition of Wnt/β‐catenin signaling	ICG‐001	Small‐molecule	N	39
		Inhibition of HIF pathway	BAH	Small‐molecule	N	41
		Inhibition of AXL pathway	BGB324	Small‐molecule	N	42
	Protein level	Competitive binding with IL‐36 receptors	Antibodies against IL36R	Antibody	N	44
		Induction of high tittered antibodies to IL‐12 and IL‐23	p40 peptide based vaccine	Peptide	N	45
		Reduction of IL‐13 and TGF‐β levels	pXYCYT:Hsp65	Bacteria	N	46
Cellular level	Myofibroblasts	Suppression on activation of myofibroblasts	Triptolide	Small‐molecule	N	48
		Disturbance of myofibroblast function	GED‐0507‐34 Levo	Small‐molecule	N	49
		Inhibition of myofibroblast accumulation and autophagy potentiation	AMA0825	Small‐molecule	N	50
		Inhibition of human colonic myofibroblast proliferation was reduced	Ang (1–7); Captopril	Small‐molecule	N	51
	Fibroblasts	Inhibition of fibroblasts proliferation	Pirfenidone	Small‐molecule	N	53
		Inhibition of accelerated fibroblast migration	Vitamin D	Small‐molecule	N	54
		Inhibition of fibroblast proliferation and activation	Wu‐Mei‐Wan	A traditional Chinese herb	N	55
Tissue level		Neutralization of excessive MMP‐9	Anti‐MMP‐9 antibody	Antibody	N	59
		Regulation of TIMP/MMP balance	Thalidomide	Small‐molecule	N	60
		ECM homeostasis reconstitution	Anti‐FAP antibody	Antibody	N	61
		Reduction in ROS levels	D‐CeO2 nanozyme	Small‐molecule	Dextran‐coated nanoparticle	63

Abbreviations: ACE‐I, angiotensin converting enzyme inhibitors; FAP, fibroblast activating protein; MMP, matrix metalloproteinase; MoA, mechanism of action; TIMP, tissue inhibitors of metalloproteinases.