Vitamin D Receptor Regulates Liver Regeneration After Partial Hepatectomy in Male Mice.
Endocrinology
; 165(8)2024 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-38963813
ABSTRACT
Vitamin D signals through the vitamin D receptor (VDR) to induce its end-organ effects. Hepatic stellate cells control development of liver fibrosis in response to stressors and vitamin D signaling decreases fibrogenesis. VDR expression in hepatocytes is low in healthy liver, and the role of VDR in hepatocyte proliferation is unclear. Hepatocyte-VDR null mice (hVDR) were used to assess the role of VDR and vitamin D signaling in hepatic regeneration. hVDR mice have impaired liver regeneration and impaired hepatocyte proliferation associated with significant differential changes in bile salts. Notably, mice lacking hepatocyte VDR had significant increases in expression of conjugated bile acids after partial hepatectomy, consistent with failure to normalize hepatic function by the 14-day time point tested. Real-time PCR of hVDR and control livers showed significant changes in expression of cell-cycle genes including cyclins D1 and E1 and cyclin-dependent kinase 2. Gene expression profiling of hepatocytes treated with vitamin D or control showed regulation of groups of genes involved in liver proliferation, hepatitis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death. Together, these studies demonstrate an important functional role for VDR in hepatocytes during liver regeneration. Combined with the known profibrotic effects of impaired VDR signaling in stellate cells, the studies provide a mechanism whereby vitamin D deficiency would both reduce hepatocyte proliferation and permit fibrosis, leading to significant liver compromise.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bile Acids and Salts
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Receptors, Calcitriol
/
Mice, Knockout
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Hepatocytes
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Cell Proliferation
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Hepatectomy
/
Liver Regeneration
Limits:
Animals
Language:
En
Journal:
Endocrinology
Year:
2024
Document type:
Article
Affiliation country: