920 Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-deficient mice

Hayashi, Hideki; Nagaki, Masahito; Imose, Motoaki; Osawa, Yosuke; Naiki, Taku; Satake, Shinichi; Imao, Motohiro; Kimura, Kiminori; Moriwaki, Hisataka

doi:10.1016/s0270-9139(03)80958-8

Cited by 7 publications

(7 citation statements)

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“…Consistent with the ability of TNF-␣ to induce IL-6 (14, 27), the rise of TNF-␣ in KC-competent mice was paralleled by an increase of serum IL-6, whereas this autocrine effect was missing in KC-depleted mice. Although TNF-␣-deficient mice showed normal liver regeneration (16,18), TNF-␣ has been regarded as an important promoter of hepatocyte proliferation (22). In support of this view, studies using antibodies against TNF-␣ have demonstrated a reduction of hepatocyte proliferation (2,33).…”

Section: Discussionmentioning

confidence: 99%

Loss of NF-κB activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy

Abshagen¹,

Eipel²,

Kalff³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kupffer cells (KCs) are located in the liver sinusoids adjacent to hepatocytes and are capable of producing important growth-regulating mediators that exert both stimulatory and inhibitory influences on hepatocyte proliferation by paracrine mechanisms. To elucidate the overall effect of KC depletion on liver regeneration, mice were selectively and long-standing depleted of KCs by liposome-encapsulated dichloromethylene diphosphonate. Using in vivo fluorescence microscopy, immunohistochemistry, Western blot analysis, and NF-kappaB transcription factor DNA binding activity and cytokine assays, we analyzed livers of KC-depleted and KC-competent mice at days 3, 5, and 8 after partial (i.e., 68%) hepatectomy (PH). Selective KC elimination delayed cell proliferation, as indicated by significantly reduced PCNA and cyclin B1 protein expression in liver tissue at day 3 after PH. This was associated with a lower liver weight at day 8 upon PH. Resection-associated activation of NF-kappaB with translocation into parenchymal and nonparenchymal cell nuclei was diminished in livers of KC-depleted mice, primarily at day 3 after PH. KC-depleted mice further lacked the resection-induced rise in TNF-alpha and IL-6 serum concentrations. These findings imply that KCs play a stimulatory role in liver regeneration, mainly by activating NF-kappaB with influence on the cell cycle and by enhancing expression of the proliferative cytokines TNF-alpha and IL-6.

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Section: Discussionmentioning

confidence: 99%

Loss of NF-κB activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy

Abshagen¹,

Eipel²,

Kalff³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The main cytokines studied are tumor necrosis factor (TNF) and Interleukin-6 (IL-6). TNF receptor-1 KO mice have several defects after partial hepatectomy, but mice lacking the TNF ligand regenerate normally, indicating that TNF acts redundantly with other ligands that bind the receptor (Fujita et al 2001;Hayashi et al 2005). TNF and other ligands of the TNF receptor are thought to activate NF-B signaling in Kupffer cells, which results in up-regulation of IL-6 expression (Kirillova et al 1999).…”

Section: Innate Immunity and Cytokine Signalingmentioning

confidence: 99%

Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine

Stoick-Cooper¹,

Moon²,

Weidinger³

2007

Genes Dev.

276

278

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While all animals have evolved strategies to respond to injury and disease, their ability to functionally recover from loss of or damage to organs or appendages varies widely damage to skeletal muscle, but, unlike amphibians and fish, they fail to regenerate heart, lens, retina, or appendages. The relatively young field of regenerative medicine strives to develop therapies aimed at improving regenerative processes in humans and is predicated on >40 years of success with bone marrow transplants. Further progress will be accelerated by implementing knowledge about the molecular mechanisms that regulate regenerative processes in model organisms that naturally possess the ability to regenerate organs and/or appendages. In this review we summarize the current knowledge about the signaling pathways that regulate regeneration of amphibian and fish appendages, fish heart, and mammalian liver and skeletal muscle. While the cellular mechanisms and the cell types involved in regeneration of these systems vary widely, it is evident that shared signals are involved in tissue regeneration. Signals provided by the immune system appear to act as triggers of many regenerative processes. Subsequently, pathways that are best known for their importance in regulating embryonic development, in particular fibroblast growth factor (FGF) and Wnt/␤-catenin signaling (as well as others), are required for progenitor cell formation or activation and for cell proliferation and specification leading to tissue regrowth. Experimental activation of these pathways or interference with signals that inhibit regenerative processes can augment or even trigger regeneration in certain contexts.

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“…[25][26][27] Some of the upregulated genes are absolutely necessary for regeneration to occur, [28][29][30] whereas others show degrees of redundancy. 28,31 The genes involved in liver regeneration fall into three categories: cytokines, growth factors, and genes with metabolic functions. 32 The trigger of the liver regeneration cascade is thought to be the result of shear stress-induced nitric oxide (NO) and prostaglandins (PGs) 33,34 after the increase in the blood flow-to-liver mass ratio after liver resection.…”

Section: Liver Regeneration After Hepatectomymentioning

confidence: 99%

Liver Regeneration and Tumor Stimulation—A Review of Cytokine and Angiogenic Factors

Christophi

Harun

Fifis

2008

Journal of Gastrointestinal Surgery

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Liver resection for metastatic (colorectal carcinoma) tumors is often followed by a significant incidence of tumor recurrence. Cellular and molecular changes resulting from hepatectomy and the subsequent liver regeneration process may influence the kinetics of tumor growth and contribute to recurrence. Clinical and experimental evidence suggests that factors involved in liver regeneration may also stimulate the growth of occult tumors and the reactivation of dormant micrometastases. An understanding of the underlying changes may enable alternative strategies to minimize tumor recurrence and improve patient survival after hepatectomy.

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920 Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-deficient mice

Cited by 7 publications

References 0 publications

Loss of NF-κB activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy

Loss of NF-κB activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy

Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine

Liver Regeneration and Tumor Stimulation—A Review of Cytokine and Angiogenic Factors

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