Lack of RAMP1 Signaling Suppresses Liver Regeneration and Angiogenesis Following Partial Hepatectomy in Mice.
In Vivo
; 38(5): 2261-2270, 2024.
Article
in En
| MEDLINE
| ID: mdl-39187322
ABSTRACT
BACKGROUND/AIM:
The liver effectively restores both size and function following partial hepatectomy (PHx). Angiogenesis is crucial for the repair and regeneration of liver tissue post-PHx. Calcitonin gene-related peptide (CGRP) released from sensory nerves and its receptor-receptor activity-modifying protein 1 (RAMP1) are involved in angiogenesis. This study aimed to assess the role of RAMP1 signaling in angiogenesis during liver regeneration following PHx. MATERIALS ANDMETHODS:
RAMP1 deficient (RAMP1-/-) and wild-type (WT) mice were subjected to PHx.RESULTS:
RAMP1-/- mice demonstrated delayed liver regeneration, indicated by lower liver-to-body weight ratios compared to WT mice. This was associated with lower levels of Ki67+ hepatocytes and hepatic trophic growth factors. Additionally, RAMP1-/- mice exhibited lower levels of endothelial cell markers, including CD31, compared to WT mice. This reduction was associated with reduced levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor 3 (VEGFR3). In WT mice with PHx, the administration of a VEGFR3 inhibitor reduced the liver-to-body weight ratio, Ki67+ hepatocytes, and VEGF-C/VEGFR3 expression levels in the liver compared to those in the vehicle-treated group.CONCLUSION:
The deletion of RAMP1 signaling suppresses liver regeneration and angiogenesis through VEGFR3. Specific activation of RAMP1 signaling may represent a potential therapeutic strategy for liver regeneration following PHx.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Mice, Knockout
/
Neovascularization, Physiologic
/
Receptor Activity-Modifying Protein 1
/
Hepatectomy
/
Liver Regeneration
Limits:
Animals
Language:
En
Journal:
In Vivo
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
Japan
Country of publication:
Greece