{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:18:16Z","timestamp":1787725096737,"version":"build-2784847793"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2021R1I1A3057140"],"award-info":[{"award-number":["NRF-2021R1I1A3057140"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["RS-2023-00243582"],"award-info":[{"award-number":["RS-2023-00243582"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Nephrology Research Foundation","award":["NRF-2021R1I1A3057140"],"award-info":[{"award-number":["NRF-2021R1I1A3057140"]}]},{"name":"Korean Nephrology Research Foundation","award":["RS-2023-00243582"],"award-info":[{"award-number":["RS-2023-00243582"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder. While metformin has demonstrated the ability to inhibit cyst growth in animal models of ADPKD via activation of adenosine monophosphate-activated protein kinase (AMPK), its effectiveness in humans is limited due to its low potency. This study explored the impact of HL156A, a new and more potent AMPK activator, in a mouse model of ADPKD. Methods: To investigate whether HL156A inhibits the proliferation of renal cyst cells in ADPKD in vitro, exogenous human telomerase reverse transcriptase (hTERT)-immortalized renal cyst cells from ADPKD patients were treated with HL156A, and an MTT (dimethylthiazol-diphenyltetrazolium bromide) assay was performed. To assess the cyst-inhibitory effect of HL156A in vivo, we generated Pkd1 conditional knockout (KO) mice with aquaporin 2 (AQP2)-Cre, which selectively expresses Cre recombinase in the collecting duct. The effectiveness of HL156A in inhibiting cyst growth and improving renal function was confirmed by measuring the number of cysts and blood urea nitrogen (BUN) levels in the collecting duct-specific Pkd1 KO mice. Results: When cyst cells were treated with up to 20 \u00b5M of metformin or HL156A, HL156A reduced cell viability by 25% starting at a concentration of 5 \u00b5M, whereas metformin showed no effect. When AQP2-Cre male mice were crossed with Pkd1flox\/flox female mice, and when AQP2-Cre female mice were crossed with Pkd1flox\/flox male mice, the number of litters produced by both groups was comparable. In collecting duct-specific Pkd1 KO mice, HL156A was found to inhibit cyst growth, reducing both the number and size of cysts. Furthermore, it was confirmed that kidney function improved as HL156A treatment led to a reduction in elevated BUN levels. Lastly, it was observed that the increase in AMPK phosphorylation induced by HL156A decreased ERK phosphorylation and \u03b1-SMA expression. Conclusion: HL156A has potential as a drug that can restore kidney function in ADPKD patients by inhibiting cyst growth.<\/jats:p>","DOI":"10.3390\/biom14070806","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HL156A, an AMP-Activated Protein Kinase Activator, Inhibits Cyst Growth in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Sujung","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunho","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Medical Innovation, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Taek","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Eop","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-jin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwangeon","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myunkyu","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7915-3733","authenticated-orcid":false,"given":"Jong-woo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(18)32782-X","article-title":"Autosomal dominant polycystic kidney disease","volume":"393","author":"Alam","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"F27","DOI":"10.1152\/ajprenal.00298.2021","article-title":"Metformin improves relevant disease parameters in an autosomal dominant polycystic kidney disease mouse model","volume":"322","author":"Li","year":"2022","journal-title":"Am. 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