Human Epididymis Protein 4 as a Potential Biomarker for Crohn’s Disease-Associated Intestinal Fibrosis

Abstract Human epididymis protein 4 (HE4) plays a crucial role in promoting extracellular matrix (ECM) deposition by inhibiting matrix metalloproteinase (MMP) activity. Crohn's disease (CD) often leads to intestinal fibrosis and obstruction due to chronic inflammation. This study evaluated HE4 expression in serum and intestinal tissues from CD patients, and the effects of anti-HE4 antibody in a TNBS-induced mouse model of intestinal fibrosis. HE4 levels were significantly elevated in both serum and intestinal tissues of patients with stricturing CD, correlating with increased intestinal fibrosis and wall thickness. Inhibition of HE4 expression in mice reduced serum levels of IL-6, TNF-α, and intestinal expression of key fibrotic markers, including α-SMA, COL1A1, Fibronectin. These results suggest that HE4 is a potential biomarker for CD-associated intestinal fibrosis and a promising therapeutic target to mitigate fibrosis progression in CD.