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

Sakai, Norihiro; Kamimura, Kenya; Miyamoto, Hirotaka; Ko, Masayoshi; Nagoya, Takuro; Setsu, Toru; Sakamaki, Akira; Yokoo, Takeshi; Kamimura, Hiroteru; Soki, Hiroyuki; Tokunaga, Ayako; Inamine, Tatsuo; Nakashima, Makoto; Enomoto, Hatsune; Kousaka, Kazuki; Tachiki, Hidehisa; Ohyama, Kaname; Terai, Shuji

doi:10.1007/s00535-022-01929-w

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…Consequently, letrozole was observed as a new repurposing drug that suppresses liver fibrosis-related genes, including YAP-CTGF; the in vitro suppression of these genes was observed in a volume-dependent manner. In vivo experiments using two different liver fibrosis mouse models showed a weakening effect on liver fibrosis, and we reported that along with YAP-CTGF, HSD17B13, which is involved in retinoic acid metabolism [ 108 , 109 ] and nonalcoholic fatty liver disease [ 110 ], was associated with this effect [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Letrozole has been used for breast cancer; however, a new indication for liver fibrosis has been discovered, focusing on comprehensive gene alternations in chimeric mice models with humanized hepatocytes. After 36 repositionable drugs were administrated to chimeric mice, microarray on human genes was performed and indicated that gene expression analysis was an appropriate method for screening for medicines that were effective for liver fibrosis and that LET inhibited YAP, CTGF, and TGF-β expressions and activated CYP26A1 expressions in humanized hepatocytes in chimeric mice; moreover, it ameliorated liver fibrosis in two liver fibrosis mouse models [ 49 ].…”

Section: Discovery Of Repurposing Drugs On the Basis Of Gene Expressi...mentioning

confidence: 99%

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Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs

Sakai,

Kamimura,

Terai

2023

Pharmaceutics

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Conventional drug discovery involves significant steps, time, and expenses; therefore, novel methods for drug discovery remain unmet, particularly for patients with intractable diseases. For this purpose, the drug repurposing method has been recently used to search for new therapeutic agents. Repurposed drugs are mostly previously approved drugs, which were carefully tested for their efficacy for other diseases and had their safety for the human body confirmed following careful pre-clinical trials, clinical trials, and post-marketing surveillance. Therefore, using these approved drugs for other diseases that cannot be treated using conventional therapeutic methods could save time and economic costs for testing their clinical applicability. In this review, we have summarized the methods for identifying repurposable drugs focusing on immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discovery Of Repurposing Drugs On the Basis Of Gene Expressi...mentioning

confidence: 99%

Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs

Sakai,

Kamimura,

Terai

2023

Pharmaceutics

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“…85 Letrozole has been demonstrated to ameliorate liver fibrosis by inhibiting the downstream pathway of CTGF. 86 Vismodegib was loaded onto cRGDyK-modified liposomes to inhibit the activation of HSCs by the inhibition of the hedgehog pathway. The cRGDyK-modified liposomes showed affinity to αvβ3 on aHSC in vitro and in vivo, increased accumulation on aHSCs rather than on quiescent HSCs, and inhibited the progression of fibrosis in bile duct ligatonin thioacetamide mice models (Figure 4d).…”

Section: Signaling Pathways As Anti-fibrotic Targetsmentioning

confidence: 99%

“…Umbelliferone (UMB), also known as 7‐hydroxycoumarin, demonstrated efficacy in the prevention of hepatic fibrogenesis in CCl4‐induced liver fibrosis by inhibiting TGF‐β1/Smad3 signaling and downregulating α‐SMA and collagen I expression 85 . Letrozole has been demonstrated to ameliorate liver fibrosis by inhibiting the downstream pathway of CTGF 86 . Vismodegib was loaded onto cRGDyK‐modified liposomes to inhibit the activation of HSCs by the inhibition of the hedgehog pathway.…”

Section: Hepatic Fibrosismentioning

confidence: 99%

Prospective therapeutics for intestinal and hepatic fibrosis

Zhao

et al. 2023

Bioengineering & Transla Med

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Currently, there are no effective therapies for intestinal and hepatic fibrosis representing a considerable unmet need. Breakthroughs in pathogenesis have accelerated the development of anti‐fibrotic therapeutics in recent years. Particularly, with the development of nanotechnology, the harsh environment of the gastrointestinal tract and inaccessible microenvironment of fibrotic lesions seem to be no longer considered a great barrier to the use of anti‐fibrotic drugs. In this review, we comprehensively summarize recent preclinical and clinical studies on intestinal and hepatic fibrosis. It is found that the targets for preclinical studies on intestinal fibrosis is varied, which could be divided into molecular, cellular, and tissues level, although little clinical trials are ongoing. Liver fibrosis clinical trials have focused on improving metabolic disorders, preventing the activation and proliferation of hepatic stellate cells, promoting the degradation of collagen, and reducing inflammation and cell death. At the preclinical stage, the therapeutic strategies have focused on drug targets and delivery systems. At last, promising remedies to the current challenges are based on multi‐modal synergistic and targeted delivery therapies through mesenchymal stem cells, nanotechnology, and gut‐liver axis providing useful insights into anti‐fibrotic strategies for clinical use.

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17β-hydroxysteroid dehydrogenases in the progression of nonalcoholic fatty liver disease

Wang

Peng

2023

Pharmacology & Therapeutics

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

Cited by 7 publications

References 53 publications

Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs

Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs

Prospective therapeutics for intestinal and hepatic fibrosis

17β-hydroxysteroid dehydrogenases in the progression of nonalcoholic fatty liver disease

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