Autophagy induction promotes renal cyst growth in polycystic kidney disease

Eun Ji Lee, Je Yeong Ko, Sumin Oh, Jaehee Jun, Hyowon Mun, Chae Ji Lim, Seungwoon Seo, Hyuk Wan Ko, Hyunho Kim, Yun Kyu Oh, Curie Ahn, Minyong Kang, Min Jung Kim, Kyung Hyun Yoo, Goo Taeg Oh, Jong Hoon Park

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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. Funding Sources: This work was supported by grants from the Bio & Medical Technology Development Program; the Collaborative Genome Program for Fostering New Post-Genome Industry of the NRF; the Basic Science Program.

Original languageEnglish
Article number102986
JournalEBioMedicine
Volume60
DOIs
StatePublished - Oct 2020

Keywords

  • Autophagy
  • Ift46
  • PKD
  • Polycystic kidney

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