TABLE 1.

Mechanisms and molecular pathways associated with intestinal fibrosis in 2023.

Molecular	In vitro/in vivo models	Mechanism	Reference
ECM proteins	Colon biopsies, Patients' serum	MMP‐1, ‐3, ‐14, and TIMP‐1 expression increased in fibrosis CD; Collagen types I and III leans towards degradation; Collagen type V collagen leans towards formation.	Biel C, et al 25
Interleukin‐36	Colon biopsies, Mice‐derived fibroblasts, MMP13 deficient mice	IL36R signaling pathway regulates the expression of MMP13.	Koop K, et al 26
NOX4	Colitis NOX4−/− mice	NOX4 inhibits TGF‐β‐mediated inflammation injury and fibrosis.	Lee Y, et al 30
Smad7	Smad7−/− mice	Smad7 inhibits the increase of collagen content and protein expression of α‐smooth muscle actin infibrosis.	Schuler C, et al 31
COX‐2 PEG2	TNBS‐induced mice	The expression of COX‐2 and PGE2 were increased in the inflammatory site and pre inflammatory dilated site of themice model of intestinal stenosis.	Johnson JC, et al 32
MicroRNAs	Both in vivo and in vitro studies	MiR‐155 inhibited high mobility group box transcription factor 1 (HBP1), resulting in the activation of fibrosis‐related pathway.	Aggeletopoulou I, et al 33
AGE/RAGE	Both in vivo and in vitro studies	AGE/RAGE increased in patients and DSS‐treated mice compared to controls.	Pompili S, et al 34
Nrf2/ARE	Both in vivo and in vitro studies	Nrf2 agonists prevented transformation of intestinal fibroblasts into myofibroblasts by inhibiting the TGF‐/Smad axis.	Li B, et al 35

Abbreviations: AGE/RAGE, advanced glycation end products/receptor of AGEs; ARE, antioxidant response element; CD, Crohn’s disease; COX‐2, cyclooxygenase‐2; DSS, dextran sulfate sodium; ECM, extracellular matrix; EMT, epithelial‐mesenchymal transition; MMP, matrix metalloproteinases; NOX, nicotinamide adenine dinucleotide phosphate oxidases; Nrf2, Nuclear factor erythroid 2‐related factor; PEG2, prostaglandin E2; TGF‐β, transforming growth factor‐β.