In:
Liver International, Wiley, Vol. 35, No. 4 ( 2015-04), p. 1162-1171
Abstract:
Liver regeneration is a multistage process that unfolds gradually, with different mediators acting at different stages of regeneration. Calcium (Ca 2+ ) signalling is essential for liver regeneration. In hepatocytes, Ca 2+ signalling results from the activation of inositol 1,4,5‐trisphosphate receptors (InsP 3 R) of which two of the three known isoforms are expressed (InsP 3 R‐I and InsP 3 R‐ II ). Here, we investigated the role of the InsP 3 R‐I‐dependent Ca 2+ signals in hepatic proliferation during liver regeneration. Methods Partial hepatectomy ( HX ) in combination with knockdown of InsP 3 R‐I (Adsi RNA ‐I) was used to evaluate the role of InsP 3 R‐I on liver regeneration and hepatocyte proliferation, as assessed by liver to body mass ratio, PCNA expression, immunoblots and measurements of intracellular Ca 2+ signalling. Results Adsi RNA ‐I efficiently infected the liver as demonstrated by the expression of β‐galactosidase throughout the liver lobules. Moreover, this construct selectively and efficiently reduced the expression of InsP 3 R‐I, as evaluated by immunoblots. Expression of Adsi RNA ‐I in liver decreased peak Ca 2+ amplitude induced by vasopressin in isolated hepatocytes 2 days after HX . Reduced InsP 3 R‐I expression prior to HX also delayed liver regeneration, as measured by liver to body weight ratio, and reduced hepatocyte proliferation, as evaluated by PCNA staining, at the same time point. At later stages of regeneration, control hepatocytes showed a decreased expression of InsP 3 R, as well as reduced InsP 3 R‐mediated Ca 2+ signalling, events that did not affect liver growth. Conclusion Together, these results show that InsP 3 R‐I‐dependent Ca 2+ signalling is an early triggering pathway required for liver regeneration.
Type of Medium:
Online Resource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2015.35.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2124684-1
