ArticleThe American journal of pathology2018
Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease.
Article in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling.Hepatology (Baltimore, Md.) · 2025Article
- Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.Biomolecules & therapeutics · 2024Review
- HDAC6 inhibition: a significant potential regulator and therapeutic option to translate into clinical practice in renal transplantation.Frontiers in immunology · 2023Review
- Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt.Oncology reports · 2022Article
- Polycystic Liver Disease: Advances in Understanding and Treatment.Annual review of pathology · 2022Review
- Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases.Frontiers in pharmacology · 2022Review
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Review
- Synthetic Conjugates of Ursodeoxycholic Acid Inhibit Cystogenesis in Experimental Models of Polycystic Liver Disease.Hepatology (Baltimore, Md.) · 2021Article
- SPHK1 deficiency protects mice from acetaminophen-induced ER stress and mitochondrial permeability transition.Cell death and differentiation · 2020Article
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatic cystogenesis in polycystic liver disease (PLD) is associated with abnormalities in multiple cellular processes, including elevated cAMP and overexpression of histone deacetylase 6 (HDAC6). Disease progression in polycystic kidney (PCK) rats (an animal model of PLD) is attenuated by inhibition of either cAMP production or HDAC6. Therefore, we hypothesized that concurrent targeting of HDAC6 and cAMP would synergistically reduce cyst growth. Changes in hepatorenal cystogenesis were examined in PCK rats treated with a pan-HDAC inhibitor, panobinostat; three specific HDAC6 inhibitors, ACY-1215, ACY-738, and ACY-241; and a combination of ACY-1215 and the somatostatin receptor analogue, pasireotide. We also assessed effects of ACY-1215 and pasireotide alone and in combination on cell proliferation, cAMP production, and expression of acetylated α-tubulin in vitro in cultured cholangiocytes and the length of primary cilia and the frequency of ciliated cholangiocytes in vivo in PCK rats. Panobinostat and all three HDAC6 inhibitors decreased hepatorenal cystogenesis in PCK rats. ACY-1215 was more effective than other HDAC inhibitors and was chosen for combinational treatment. ACY-1215 + pasireotide combination synergistically reduced cyst growth and increased length of primary cilia in PCK rats. In cultured cystic cholangiocytes, ACY-1215 + pasireotide combination concurrently decreased cell proliferation and inhibited cAMP levels. These data suggest that the combination of drugs that inhibit HDAC6 and cAMP may be an effective therapy for PLD.
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