Remodelling of calcium signalling during liver regeneration in the rat

Nicou, Alexandra; Serrière, Valérie; Hilly, Mauricette; Prigent, Sylvie; Combettes, Laurent; Guillon, Gilles; Tordjmann, Thierry

doi:10.1016/j.jhep.2006.08.014

Cited by 31 publications

(40 citation statements)

References 49 publications

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“…Extracellular nucleotide-mediated activation of P2Y2 purinergic receptors induce calcium signaling via activation of phospholipase C-and inositol triphosphate-3-dependent calcium release from intracellular stores. Recent studies have defined the functional significance of calcium signaling for efficient hepatocyte cell cycle progression from G 0 to G 1 and S phases in regenerating livers (15,38,52). Among the many intracellular mitogenic targets of calcium signaling, p44/42 ERK MAPKs are well-known mediators of hepatocyte cell cycle progression at the G 1 phase and S phase entry (9,24,57,65).…”

Section: Discussionmentioning

confidence: 99%

P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy

Tackett

Sun

Mei

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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cellular nucleotides via activation of P2 purinergic receptors influence hepatocyte proliferation and liver regeneration in response to 70% partial hepatectomy (PH). Adult hepatocytes express multiple P2Y (G protein-coupled) and P2X (ligand-gated ion channels) purinergic receptor subtypes. However, the identity of key receptor subtype(s) important for efficient hepatocyte proliferation in regenerating livers remains unknown. To evaluate the impact of P2Y2 purinergic receptor-mediated signaling on hepatocyte proliferation in regenerating livers, wild-type (WT) and P2Y2 purinergic receptor knockout (P2Y2Ϫ/Ϫ) mice were subjected to 70% PH. Liver tissues were analyzed for activation of early events critical for hepatocyte priming and subsequent cell cycle progression. Our findings suggest that early activation of p42/44 ERK MAPK (5 min), early growth response-1 (Egr-1) and activator protein-1 (AP-1) DNA-binding activity (30 min), and subsequent hepatocyte proliferation (24 -72 h) in response to 70% PH were impaired in P2Y2Ϫ/Ϫ mice. Interestingly, early induction of cytokines (TNF-␣, IL-6) and cytokine-mediated signaling (NF-B, STAT-3) were intact in P2Y2Ϫ/Ϫ remnant livers, uncovering the importance of cytokine-independent and nucleotidedependent early priming events critical for subsequent hepatocyte proliferation in regenerating livers. Hepatocytes isolated from the WT and P2Y2Ϫ/Ϫ mice were treated with ATP or ATP␥S for 5-120 min and 12-24 h. Extracellular ATP alone, via activation of P2Y2 purinergic receptors, was sufficient to induce ERK phosphorylation, Egr-1 protein expression, and key cyclins and cell cycle progression of hepatocytes in vitro. Collectively, these findings highlight the functional significance of P2Y2 purinergic receptor activation for efficient hepatocyte priming and proliferation in response to PH. extracellular ATP; P2Y2 purinergic receptors; partial hepatectomy; hepatocyte proliferation; liver regeneration LIVER REGENERATION IN RESPONSE to partial hepatectomy (PH) is a highly coordinated process involving a complex interplay of multiple humoral factors and integration of cell signaling in parenchymal and nonparenchymal cells (45). In response to PH, adult hepatocytes are "reprogrammed" to undergo cell cycle progression and proliferation until tissue restitution is achieved. The factor(s) that trigger cell cycle progression of hepatocytes in response to PH as well as cellular events that play a role in the reestablishment of quiescence upon the completion of liver growth are not well understood.In response to 70% PH, the remnant livers are subjected to elevated shear stress and trigger the release of factors believed to play key roles in the initiation of proliferative response in hepatocytes (1, 15, 60). Cellular stress including shear stress is a potent trigger for ATP release. Extracellular ATP, via the activation of cell surface P2 purinergic receptors, influences cell signaling, activation of transcription factors, and gene expression (5, 18). In recent years, extracellular ATP is begin...

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Section: Discussionmentioning

confidence: 99%

P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy

Tackett

Sun

Mei

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Calcium ions have been involved in left-right patterning of embryos in zebrafish, Xenopus laevis and mouse (McGrath et al, 2003;Kreiling et al, 2008;Lewis et al, 2009), in left-right determination by means of Notch signaling in chick embryos (Raya et al, 2004), and in the mediation of morphogenetic movements during neural tube formation in axolotl (Moran, 1990). Although no exact data exist on whether Ca 2þ ion kinetics have a specific function in tissue regeneration in vivo, various in vitro studies have suggested that Ca 2þ ions/channels are necessary for this process (Unlu et al, 2002;Nicou et al, 2007). Recent work from our group has demonstrated that inhibition of voltage-gated Ca 2þ channels impairs directional cell migration of osteoblast-like cells in vitro.…”

Section: Calciummentioning

confidence: 99%

Ion imaging during axolotl tail regeneration in vivo

Özkucur

Epperlein

Funk

2010

Developmental Dynamics

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Several studies have reported that endogenous ion currents are involved in a wide range of biological processes from single cell and tissue behavior to regeneration. Various methods are used to assess intracellular and local ion dynamics in biological systems, e.g., patch clamping and vibrating probes. Here, we introduce an approach to detect ion kinetics in vivo using a noninvasive method that can electrophysiologically characterize an entire experimental tissue region or organism. Ion-specific vital dyes have been successfully used for live imaging of intracellular ion dynamics in vitro. Here, we demonstrate that cellular pH, cell membrane potential, calcium, sodium and potassium can be monitored in vivo during tail regeneration in the axolotl (Ambystoma mexicanum) using ion-specific vital dyes. Thus, we suggest that ion-specific vital dyes can be a powerful tool to obtain electrophysiological data during crucial biological events in vivo.

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“…Twenty-four hours after PH the PC regions remained richer in V1a receptors with a significantly higher PC/PP gradient in hepatectomized rats than in shamoperated rats, caused by a greater loss of these receptors in the PP than in the PC area. The same authors found a similar predominant distribution of the type II D-myoinositol 1,4,5-trisphosphate (InsP3) receptor in the PC region in control rats and also a decrease in the expression of this receptor in the PP areas at 24 h after PH, resulting in an increased PC/PP gradient for type II InsP3 receptor in the regenerating liver [76] . The fact that the downregulation of both V1a and type II InsP3 receptors occurs primarily at the periphery of the lobule could be related to the cell cycle progression of hepatocytes, since the time point of the hepatocyte desensitization to calcium-mobilizing agonists 24 h after PH coincides with the peak of DNA synthesis ( fig.…”

Section: Calcium Signallingmentioning

confidence: 75%

Liver Regeneration: Focus on Cell Types and Topographic Differences

Kandilis

Koskinas²,

Tiniakos³

et al. 2009

Eur Surg Res

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Background/Aims: The liver has a remarkable capacity to regenerate after injury or resection. The aim of the current review is to outline the morphological changes at the cellular level and the intralobular differences during the regenerative response after partial hepatectomy. Methods: Relevant studies were reviewed using the Medline database. Results: At 24 h after partial hepatectomy, many alterations between the periportal and pericentral regions of the hepatic lobule occur, which coincide with the peak of hepatocellular proliferation in the periportal areas. Questions unanswered involve the precise role of Kupffer cells and whether the regenerative process is characterized by a net increase in the number of lobules or by an increase in the size of the existing lobules. Conclusions: Liver regeneration has been studied for many years, but further research is essential, since in-depth knowledge of the mechanisms that govern the regenerative process may expand the treatment options in patients with hepatic disease.

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Remodelling of calcium signalling during liver regeneration in the rat

Cited by 31 publications

References 49 publications

P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy

P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy

Ion imaging during axolotl tail regeneration in vivo

Liver Regeneration: Focus on Cell Types and Topographic Differences

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