Calcium signalling from the type I inositol 1, 4, 5‐trisphosphate receptor is required at early phase of liver regeneration. (2nd June 2014)

• Record Type: Journal Article
• 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
• Is Part Of: Liver international. Volume 35:Number 4(2015:Apr.)
• Page Start: 1162
• Page End: 1171
• Publication Date: 2014-06-02
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12587
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12587-abs-0001"> <title>Abstract</title> <sec id="liv12587-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Liver regeneration is a multistage process that unfolds gradually, with different mediators acting at different stages of regeneration. Calcium (Ca<sup>2+</sup>) signalling is essential for liver regeneration. In hepatocytes, Ca<sup>2+</sup> signalling results from the activation of inositol 1, 4, 5‐trisphosphate receptors (InsP<sub>3</sub>R) of which two of the three known isoforms are expressed (InsP<sub>3</sub>R‐I and InsP<sub>3</sub>R‐II). Here, we investigated the role of the InsP<sub>3</sub>R‐I‐dependent Ca<sup>2+</sup> signals in hepatic proliferation during liver regeneration.</p> </sec> <sec id="liv12587-sec-0002" sec-type="section"> <title>Methods</title> <p>Partial hepatectomy (HX) in combination with knockdown of InsP<sub>3</sub>R‐I (AdsiRNA‐I) was used to evaluate the role of InsP<sub>3</sub>R‐I on liver regeneration and hepatocyte proliferation, as assessed by liver to body mass ratio, PCNA expression, immunoblots and measurements of intracellular Ca<sup>2+</sup> signalling.</p> </sec> <sec id="liv12587-sec-0003" sec-type="section"> <title>Results</title> <p>AdsiRNA‐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<sub>3</sub>R‐I, as evaluated by immunoblots. Expression of AdsiRNA‐I in liver decreased peak Ca<sup>2+</sup> amplitude induced by vasopressin in isolated hepatocytes 2 days after HX. Reduced InsP<sub>3</sub>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<sub>3</sub>R, as well as reduced InsP<sub>3</sub>R‐mediated Ca<sup>2+</sup> signalling, events that did not affect liver growth.</p> </sec> <sec id="liv12587-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Together, these results show that InsP<sub>3</sub>R‐I‐dependent Ca<sup>2+</sup> signalling is an early triggering pathway required for liver regeneration.</p> </sec> </abstract>