New insights into the role of HNF-1ß in kidney (patho)physiology.
Pediatr Nephrol
; 34(8): 1325-1335, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-29961928
ABSTRACT
Hepatocyte nuclear factor-1ß (HNF-1ß) is an essential transcription factor that regulates the development and function of epithelia in the kidney, liver, pancreas, and genitourinary tract. Humans who carry HNF1B mutations develop heterogeneous renal abnormalities, including multicystic dysplastic kidneys, glomerulocystic kidney disease, renal agenesis, renal hypoplasia, and renal interstitial fibrosis. In the embryonic kidney, HNF-1ß is required for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation. Ablation of mouse Hnf1b in nephron progenitors causes defective tubulogenesis, whereas later inactivation in elongating tubules leads to cyst formation due to downregulation of cystic disease genes, including Umod, Pkhd1, and Pkd2. In the adult kidney, HNF-1ß controls the expression of genes required for intrarenal metabolism and solute transport by tubular epithelial cells. Tubular abnormalities observed in HNF-1ß nephropathy include hyperuricemia with or without gout, hypokalemia, hypomagnesemia, and polyuria. Recent studies have identified novel post-transcriptional and post-translational regulatory mechanisms that control HNF-1ß expression and activity, including the miRNA cluster miR17 â¼ 92 and the interacting proteins PCBD1 and zyxin. Further understanding of the molecular mechanisms upstream and downstream of HNF-1ß may lead to the development of new therapeutic approaches in cystic kidney disease and other HNF1B-related renal diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación del Desarrollo de la Expresión Génica
/
Urotelio
/
Enfermedades Renales Quísticas
/
Factor Nuclear 1-beta del Hepatocito
/
Túbulos Renales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Pediatr Nephrol
Asunto de la revista:
NEFROLOGIA
/
PEDIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos