Hepatocyte HIF2α Downregulates the Urea Cycle Through Suppression of HNF4α
Marc T Cantwell, Marwa O El-Derany, Raja Gopal Reddy Mooli, Sadeesh K Ramakrishnan, Yatrik M Shah · 2026
Read Hepatocyte HIF2α Downregulates the Urea Cycle Through Suppression of HNF4α by Marc T Cantwell, Marwa O El-Derany, Raja Gopal Reddy Mooli, Sadeesh K Ramakrishnan, Yatrik M Shah (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13393581.txt.
Description
Marc T Cantwell, Marwa O El-Derany, Raja Gopal Reddy Mooli, Sadeesh K Ramakrishnan, and Yatrik M Shah traced how low oxygen inside liver cells shuts down the urea cycle. That pathway detoxifies ammonia into urea. Fatty liver disease involves chronic oxygen shortage, and the oxygen sensor HIF2-alpha drives severe inflammation and scarring in mouse models. Working in mouse hepatocytes and in liver tissue from mice bred for chronic low oxygen, the team hunted for nitrogen handling faults.
The urea cycle proved significantly depressed in a HIF2-alpha-dependent manner, and ammonia duly climbed. Control sits with HNF4-alpha, the master regulator of mature liver identity, which HIF2-alpha suppresses. With the master switch dimmed, several liver-specific pathways falter together. The authors suggest blocking HIF2-alpha could preserve full hepatocyte function, while noting that exactly how it represses its target remains an open investigation.
Catalog record
| CREATOR | Marc T Cantwell, Marwa O El-Derany, Raja Gopal Reddy Mooli, Sadeesh K Ramakrishnan, Yatrik M Shah |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 30922 |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |