{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Choi SI"],"funding":["Ministry of Education","Ministry of Health & Welfare, Republic of Korea"],"pagination":["10343-10355"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7521267"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(18)"],"pubmed_abstract":["Granular corneal dystrophy type 2 (GCD2) is the most common form of transforming growth factor β-induced (TGFBI) gene-linked corneal dystrophy and is pathologically characterized by the corneal deposition of mutant-TGFBIp. The defective autophagic degradation of pathogenic mutant-TGFBIp has been shown in GCD2; however, its exact mechanisms are unknown. To address this, we investigated lysosomal functions using corneal fibroblasts. Levels of cathepsins K and L (CTSK and CTSL) were significantly decreased in GCD2 cells, but of cathepsins B and D (CTSB and CTSD) did not change. The maturation of the pro-enzymes to their active forms (CTSB, CTSK and CTSL) was inhibited in GCD2 cells. CTSL enzymes directly degraded both LC3 (autophagosomes marker) and mutant-TGFBIp. Exogenous CTSL expression dr"],"journal":["Journal of cellular and molecular medicine"],"pubmed_title":["Lysosomal dysfunction of corneal fibroblasts underlies the pathogenesis of Granular Corneal Dystrophy Type 2 and can be rescued by TFEB."],"pmcid":["PMC7521267"],"funding_grant_id":["NRF-2016R1D1A1B03934794","HI16C1009"],"pubmed_authors":["Choi SI","Kim EK","Woo JH"],"additional_accession":[]},"is_claimable":false,"name":"Lysosomal dysfunction of corneal fibroblasts underlies the pathogenesis of Granular Corneal Dystrophy Type 2 and can be rescued by TFEB.","description":"Granular corneal dystrophy type 2 (GCD2) is the most common form of transforming growth factor β-induced (TGFBI) gene-linked corneal dystrophy and is pathologically characterized by the corneal deposition of mutant-TGFBIp. The defective autophagic degradation of pathogenic mutant-TGFBIp has been shown in GCD2; however, its exact mechanisms are unknown. To address this, we investigated lysosomal functions using corneal fibroblasts. Levels of cathepsins K and L (CTSK and CTSL) were significantly decreased in GCD2 cells, but of cathepsins B and D (CTSB and CTSD) did not change. The maturation of the pro-enzymes to their active forms (CTSB, CTSK and CTSL) was inhibited in GCD2 cells. CTSL enzymes directly degraded both LC3 (autophagosomes marker) and mutant-TGFBIp. Exogenous CTSL expression dr","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Sep","modification":"2025-04-19T15:06:03.16Z","creation":"2020-10-08T07:21:46Z"},"accession":"S-EPMC7521267","cross_references":{"pubmed":["32667742"],"doi":["10.1111/jcmm.15646"]}}