RGD Reference Report - Calcium signalling from the type I inositol 1,4,5-trisphosphate receptor is required at early phase of liver regeneration. - Rat Genome Database

RGD Reference Report - Calcium signalling from the type I inositol 1,4,5-trisphosphate receptor is required at early phase of liver regeneration. - Rat Genome Database

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General

Calcium signalling from the type I inositol 1,4,5-trisphosphate receptor is required at early phase of liver regeneration.
Authors:	Oliveira, André G Andrade, Viviane A Guimarães, Erika S Florentino, Rodrigo M Sousa, Pedro A Marques, Pedro E Melo, Flávia M Ortega, Miguel J Menezes, Gustavo B Leite, M Fatima
Citation:	Oliveira AG, etal., Liver Int. 2015 Apr;35(4):1162-71. doi: 10.1111/liv.12587. Epub 2014 Jun 2.
RGD ID:	13793384
Pubmed:	PMID:24814243 (View Abstract at PubMed)
DOI:	DOI:10.1111/liv.12587 (Journal Full-text)
BACKGROUND & AIMS: 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 (InsP3 R) of which two of the three known isoforms are expressed (InsP3 R-I and InsP3 R-II). Here, we investigated the role of the InsP3 R-I-dependent Ca(2+) signals in hepatic proliferation during liver regeneration. METHODS: Partial hepatectomy (HX) in combination with knockdown of InsP3 R-I (AdsiRNA-I) was used to evaluate the role of InsP3 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: AdsiRNA-I efficiently infected the liver as demonstrated by the expression of ß-galactosidase throughout the liver lobules. Moreover, this construct selectively and efficiently reduced the expression of InsP3 R-I, as evaluated by immunoblots. Expression of AdsiRNA-I in liver decreased peak Ca(2+) amplitude induced by vasopressin in isolated hepatocytes 2 days after HX. Reduced InsP3 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 InsP3 R, as well as reduced InsP3 R-mediated Ca(2+) signalling, events that did not affect liver growth. CONCLUSION: Together, these results show that InsP3 R-I-dependent Ca(2+) signalling is an early triggering pathway required for liver regeneration.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
liver regeneration		IMP		13793384		RGD
positive regulation of cytosolic calcium ion concentration		IMP		13793384		RGD
positive regulation of hepatocyte proliferation		IMP		13793384		RGD

Objects Annotated

Genes (Rattus norvegicus)

Itpr1 (inositol 1,4,5-trisphosphate receptor, type 1)

Additional Information