The induction of the immediate-early-genes Egr-1, PAI-1 and PRL-1 during liver regeneration in surgical models is related to increased portal flow

Müeller, Lars; Bröering, Dieter C.; Meyer, J.; Vashist, Yogesh K.; Goettsche, Juliane; Wilms, Christian; Rogiers, Xavier

doi:10.1016/s0168-8278(02)00238-6

Cited by 55 publications

(90 citation statements)

References 35 publications

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“…This mass loss was fully compensated by the rapid weight gain observable in case of the PVNL lobes; consequently, the total liver weight remained constant. The weight gain in PVNL lobes reached a plateau phase between the fifth and seventh days at approximately 329% of the baseline, which finding was consistent with previously published data [5,21,22]. However, the specific alterations in hepatic lobar structure have not been assessed so far.…”

Section: Discussionsupporting

confidence: 89%

Alterations in hepatic lobar function in regenerating rat liver

Fülöp

Budai

Czigány

et al. 2015

Journal of Surgical Research

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Section: Discussionsupporting

confidence: 89%

Alterations in hepatic lobar function in regenerating rat liver

Fülöp

Budai

Czigány

et al. 2015

Journal of Surgical Research

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“…In response to 70% PH, hepatocytes in remnant livers are the first to enter cell cycle and transition from G 0 to G 1 , which is characterized by the induction of immediate early genes, most notably Egr-1 (51,54,64). Partial hepatectomy activated a robust and early induction of Egr-1 protein expression (4.0-fold) in remnant livers, which was significantly attenuated in P2Y2Ϫ/Ϫ (1.6-fold) (Fig.…”

Section: Immediate Early Genes Egr-1 and Ap-1 Dna-binding Activity Ismentioning

confidence: 90%

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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“…In addition, expression of EGR-1 is co-regulated with acute-phase response genes during inflammation in the eye (15), liver (36), and lung (39). Moreover, EGR-1 expression is upregulated as part of the mammary response to milk accumulation (53), and it is also upregulated and thought to mediate immediate early changes in blood flow during liver remodeling (41). Therefore, we propose that an acute-phase response involving EGR-1 is induced after as little as 3.5 h of milk accumulation (as seen in the 2ϫ gland), and that this response is downregulated by removal of milk from the gland (as seen in the 4ϫ gland).…”

Section: Acute Response: Genes and Functionsmentioning

confidence: 99%