Gagliotta, Salvatore (2025) Investigating the role of TFEB in Tuberous Sclerosis Complex associated-kidney pathology using novel human kidney organoid models. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Investigating the role of TFEB in Tuberous Sclerosis Complex associated-kidney pathology using novel human kidney organoid models |
| Autori: | Autore Email Gagliotta, Salvatore salvatore.gagliotta@unina.it |
| Data: | 10 Dicembre 2025 |
| Numero di pagine: | 114 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Scuola Superiore Meridionale |
| Dottorato: | Genomic and experimental medicine |
| Ciclo di dottorato: | 37 |
| Coordinatore del Corso di dottorato: | nome email Franco, Brunella franco@tigem.it |
| Tutor: | nome email Staiano, Leopoldo [non definito] |
| Data: | 10 Dicembre 2025 |
| Numero di pagine: | 114 |
| Parole chiave: | rare disease,Tuberous Sclerosis Complex,kidney disease |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 05 - Scienze biologiche > BIO/18 - Genetica Area 06 - Scienze mediche > MED/03 - Genetica medica |
| Depositato il: | 20 Gen 2026 16:27 |
| Ultima modifica: | 12 Ago 2026 05:38 |
| URI: | https://www.fedoa.unina.it/id/eprint/16873 |
Abstract
Tuberous Sclerosis Complex (TSC) is a rare autosomal dominant disorder characterized by the development of benign tumors and renal cysts across multiple organs, primarily resulting from loss-of-function mutations in the TSC1 or TSC2 genes. These mutations cause constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of cell growth and metabolism. However, the mechanisms linking mTORC1 hyperactivation to cystogenesis and tumorigenesis, particularly within the kidney, remain incompletely understood. In this study, we investigated the contribution of the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy, to TSC-associated renal pathology. Using human pluripotent stem cells (hPSCs), we generated both constitutive and inducible TSC2-deficient kidney organoids that reproduce essential aspects of human TSC kidney lesions. These models displayed mTORC1 hyperactivation, constitutive nuclear localization of TFEB, and upregulation of its downstream lysosomal–autophagic targets, including GPNMB, LAMP1, and SQSTM1.
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