Letrozole ameliorates liver fibrosis through the inhibition of the CTGF pathway and 17β-hydroxysteroid dehydrogenase 13 expression.

Norihiro SakaiKenya KamimuraHirotaka MiyamotoMasayoshi KoTakuro NagoyaToru SetsuAkira SakamakiTakeshi YokooHiroteru KamimuraHiroyuki SokiAyako TokunagaTatsuo InamineMikiro NakashimaHatsune EnomotoKazuki KousakaHidehisa TachikiKaname OhyamaShuji Terai
Published in: Journal of gastroenterology (2022)
Letrozole slowed the progression of liver fibrosis by inhibiting the Yap-Ctgf pathway. The mechanisms involved the modification of the Hsd17b13 and Cyp26a1 expressions led to the suppression of retinoic acid in the hepatocytes, which contributed to the activation of Yap-Ctgf pathway. Because of its off-target effect, letrozole could be repurposed for the treatment of liver fibrosis. The third-generation aromatase inhibitor letrozole ameliorated liver fibrosis by suppressing the Yap-Ctgf pathway by partially modifying the Hsd17b13 and Cyp26a1 expressions, which reduced the retinoic acid level in the hepatocytes. The gene expression analysis using chimeric mice with humanized liver revealed that the mechanisms are letrozole specific and, therefore, may be repurposed for the treatment of liver fibrosis.