The pathobiology of polycystic kidney disease from a metabolic viewpoint
| Autor: | Gregory G. Germino, Luis F. Menezes |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
030232 urology & nephrology Autosomal dominant polycystic kidney disease Tolvaptan urologic and male genital diseases Kidney 03 medical and health sciences 0302 clinical medicine Polycystic kidney disease Medicine Animals Humans Cyst PI3K/AKT/mTOR pathway Cystic kidney Polycystic Kidney Diseases PKD1 urogenital system business.industry Kidney metabolism medicine.disease female genital diseases and pregnancy complications 030104 developmental biology Nephrology Cancer research business Metabolic Networks and Pathways medicine.drug |
| Zdroj: | Nature reviews. Nephrology. 15(12) |
| ISSN: | 1759-507X |
| Popis: | Autosomal dominant polycystic kidney disease (ADPKD) affects an estimated 1 in 1,000 people and slowly progresses to end-stage renal disease (ESRD) in about half of these individuals. Tolvaptan, a vasopressin 2 receptor blocker, has been approved by regulatory authorities in many countries as a therapy to slow cyst growth, but additional treatments that target dysregulated signalling pathways in cystic kidney and liver are needed. Metabolic reprogramming is a prominent feature of cystic cells and a potentially important contributor to the pathophysiology of ADPKD. A number of pathways previously implicated in the pathogenesis of the disease, such as dysregulated mTOR and primary ciliary signalling, have roles in metabolic regulation and may exert their effects through this mechanism. Some of these pathways are amenable to manipulation through dietary modifications or drug therapies. Studies suggest that polycystin-1 and polycystin-2, which are encoded by PKD1 and PKD2, respectively (the genes that are mutated in >99% of patients with ADPKD), may in part affect cellular metabolism through direct effects on mitochondrial function. Mitochondrial dysfunction could alter the redox state and cellular levels of acetyl-CoA, resulting in altered histone acetylation, gene expression, cytoskeletal architecture and response to cellular stress, and in an immunological response that further promotes cyst growth and fibrosis. |
| Databáze: | OpenAIRE |
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