ANPEP and Cowden disease: APN interferes with the expression of TIMP1 and TGFB1 in IBD by targeting AdipoR2 (Fig. 4A, J-K), so emodin succinate monoethyl ester (ESME), an AdipoR2 agonist [58] possibly recedes the severity of colonic fibrosis in UC and fistulae in CD by restoring balance of TIMP1 and TGFB1.