{"doi":"10.1016/j.ebiom.2020.103043","title":"Is autophagy the culprit of cystogenesis in polycystic kidney disease?","abstract":"Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited human renal disease, results from mutations in either PKD1 or PKD2 gene. It is a progressive disease characterized by gradual cystogenesis and cyst enlargement in multiple organs, such as the kidney and liver. Despite intensive studies in the past several decades, especially after the identification of the responsible genes, the cellular and molecular mechanisms of ADPKD are still not well understood. A consensus is that increased cell proliferation is responsible for cyst formation and development. However, clinical trials with anti-proliferation drugs such as mTOR inhibitors failed to generate encouraging results in PKD patients [[1]Serra AL Poster D Kistler AD et al.Sirolimus and kidney growth in autosomal dominant polycystic kidney disease.N Engl J Med. 2010; 363: 820-829Crossref PubMed Scopus (431) Google Scholar,[2]Walz G Budde K Mannaa M et al.Everolimus in patients with autosomal dominant polycystic kidney disease.N Engl J Med. 2010; 363: 830-840Crossref PubMed Scopus (439) Google Scholar]. Although these drugs are shown to be effective in reducing cyst number and size and improving renal function in animal models. Recently, autophagy has emerged as an important mechanism in PKD, in consideration of several observations: 1) mTOR is the negative regulator of autophagy and autophagy suppression has been reported in human PKD kidneys and animal models [[3]Belibi F Zafar I Ravichandran K et al.Hypoxia-inducible factor-1alpha (HIF-1alpha) and autophagy in polycystic kidney disease (PKD).Am J Physiol Renal Physiol. 2011; 300: F1235-F1243Crossref PubMed Scopus (82) Google Scholar,[4]Shillingford JM Murcia NS Larson CH et al.The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease.Proc Natl Acad Sci U S A. 2006; 103: 5466-5471Crossref PubMed Scopus (623) Google Scholar], 2) activation of autophagy alleviates cystogenesis, 3) polycystin-1 or -2 has crosstalk with autophagy system directly or indirectly by interacting with ATG (autophagy-related gene) proteins and 4) PKD is one of the ciliopathies, while primary cilia and autophagy regulate reciprocally [5Wang S Livingston MJ Su Y Dong Z Reciprocal regulation of cilia and autophagy via the MTOR and proteasome pathways.Autophagy. 2015; 11: 607-616Crossref PubMed Scopus (90) Google Scholar, 6Tang Z Lin MG Stowe TR et al.Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites.Nature. 2013; 502: 254-257Crossref PubMed Scopus (264) Google Scholar, 7Pampliega O Orhon I Patel B et al.Functional interaction between autophagy and ciliogenesis.Nature. 2013; 502: 194-200Crossref PubMed Scopus (285) Google Scholar]. In a study reported in EBioMedicine, Lee et al [[8]Lee EJ Ko JY Oh S et al.Autophagy induction promotes renal cyst growth in polycystic kidney disease.E Bio Med. 2020; (In PressAccess available)https://10.1016/j.ebiom.2020.102986Google Scholar] made another attempt to elucidate the relationship between autophagy and PKD by taking advantage of different techniques and models. They first examined the expression profile of ATG genes using previously published microarray datasets derived from human ADPKD samples. In contrast to the previous report [[3]Belibi F Zafar I Ravichandran K et al.Hypoxia-inducible factor-1alpha (HIF-1alpha) and autophagy in polycystic kidney disease (PKD).Am J Physiol Renal Physiol. 2011; 300: F1235-F1243Crossref PubMed Scopus (82) Google Scholar], they found a high expression of almost two-thirds of ATG genes in PKD human samples. This finding encouraged them to further explore autophagy in PKD using different animal models. Ablation of ift46 specifically in collecting ducts led to PKD phenotype and activation of MAPK and mTOR signaling pathways, accompanied by a loss of cilia and increased cell proliferation and apoptosis. They also found the reduction of ATG proteins and dysfunctiona","journal":"EBioMedicine","year":2020,"id":112553,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242441,"name":"Zheng Dong","orcid":"0000-0003-3538-8095","position":1,"is_corresponding":false},{"id":532108,"name":"Shixuan Wang","orcid":"0000-0002-3088-0745","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:13:13.874980Z","pmid":"33038761","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}