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http://purl.uniprot.org/citations/33831322http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33831322http://www.w3.org/2000/01/rdf-schema#comment"Autophagy dysfunction is a hallmark of type 1 diabetes. However, the precise molecular mechanism of proteinuria-induced dysfunctional autophagy remains unclear. Herein, we investigated the role of programmed cell death 4 (PDCD4) in the regulation of autophagy in the pathogenesis of diabetic kidney disease (DKD) in vivo and in vitro. RT-qPCR, immunohistochemistry (IHC), and western blotting demonstrated an upregulation of Pdcd4 mRNA and protein in streptozotocin (STZ)-induced DKD rats, as compared to the control. In addition, IHC and western blotting of a unilateral ureteral obstruction mouse model showed an upregulation of PDCD4 in the disease group, as compared to their respective controls. IHC analysis of kidney biopsy samples of human DKD patients showed an upregulation of PDCD4 compared to the control. Western blotting of the STZ-induced DKD rat tissues displayed a low microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, as compared to the control. It was found that albumin overload in cultured PTECs upregulated the expression of PDCD4 and p62 and decreased the expression of LC3-II and autophagy-related 5 (Atg5) proteins. The knockout of Pdcd4 in cultured PTECs could reduce albumin-induced dysfunctional autophagy, as evidenced by the recovery of Atg5 and LC3-II protein. The forced expression of PDCD4 could further suppress the expression of the crucial autophagy-related gene Atg5. Evidence suggests that endogenous PDCD4 promotes proteinuria-induced dysfunctional autophagy by negatively regulating Atg5. Therefore, PDCD4 may be a potential therapeutic target in DKD."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.org/dc/terms/identifier"doi:10.1139/bcb-2021-0028"xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Lu S."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Li D."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Ren J."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Yang X."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Zhu W."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Du X."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Lan X."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Huang F."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Tian L."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Liang D."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Farooq R."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Sadiq M."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/author"Osoro E.K."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/name"Biochem Cell Biol"xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/pages"617-628"xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/title"Induction of PDCD4 by albumin in proximal tubule epithelial cells potentiates proteinuria-induced dysfunctional autophagy by negatively targeting Atg5."xsd:string
http://purl.uniprot.org/citations/33831322http://purl.uniprot.org/core/volume"99"xsd:string
http://purl.uniprot.org/citations/33831322http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33831322
http://purl.uniprot.org/citations/33831322http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33831322
http://purl.uniprot.org/uniprot/#_B3KMH8-mappedCitation-33831322http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33831322
http://purl.uniprot.org/uniprot/#_A9UGY9-mappedCitation-33831322http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33831322