한빛사 논문
Eun Ji Leea,1, Je Yeong Koa,1, Sumin Oha, Jaehee Juna, Hyowon Muna, Chae Ji Limb, Seungwoon Seob, Hyuk Wan Kod, Hyunho Kime, Yun Kyu Ohf, Curie Ahng, Minyong Kangc, Min Jung Kima, Kyung Hyun Yooa, Goo Taeg Ohb,*, Jong Hoon Parka,*
aDepartment of Biological Science, Sookmyung Women's University, Seoul 04310, Republic of Korea
bDepartment of Biology, Ewha Womans University, Seoul 03760, Republic of Korea
cDepartment of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
dDepartment of Biochemistry, Yonsei University, Seoul 03722, Republic of Korea
eCenter for Medical Innovation, Biomedical Research Institute, Seoul National University Hospital, Seoul 03082, Republic of Korea
fDepartment of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea
gDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
1These authors contributed equally to this work.
*Corresponding author.
Abstract
Background
Polycystic kidney disease (PKD) involves renal cysts arising from proliferating tubular cells. Autophagy has been recently suggested as a potential therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key negative regulator of autophagy. However, the effect of autophagy regulation on cystogenesis has not been elucidated in PKD mice.
Methods
Clinical validation was performed using GEO datasets and autosomal dominant polycystic kidney disease (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used for in vivo verifications, and additional tests were performed in vitro and in vivo using multiple autophagy drugs.
Findings
Neither autophagy stimulation nor LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a specific group of patients with ADPKD.
Interpretation
Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD.
Keywords : Polycystic kidney, PKD, Autophagy, Ift46
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