AP-2β/KCTD1 Control Distal Nephron Differentiation and Protect against Renal Fibrosis.

ABSTRACT: The developmental mechanisms that orchestrate differentiation of specific nephron segments are incompletely understood, and the factors that maintain their terminal differentiation after nephrogenesis remain largely unknown. Here, the transcription factor AP-2β is shown to be required for the differentiation of distal tubule precursors into early stage distal convoluted tubules (DCTs) during nephrogenesis. In contrast, its downstream target KCTD1 is essential for terminal differentiation of early stage DCTs into mature DCTs, and impairment of their terminal differentiation owing to lack of KCTD1 leads to a severe salt-losing tubulopathy. Moreover, sustained KCTD1 activity in the adult maintains mature DCTs in this terminally differentiated state and prevents renal fibrosis by repressing β-

SUBMITTER: Marneros AG 

PROVIDER: S-EPMC7497565 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature