Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “REGENERATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1998

Hair cell loss and regeneration after severe acoustic overstimulation in the adult pigeon.

The extent of hair cell regeneration following acoustic overstimulation severe enough to destroy tall hair cells, was determined in adult pigeons. BrdU (5-bromo-2'-deoxyuridine) was used as a proliferation marker. Recovery of hearing thresholds in each individual animal was measured over a period of up to 16 weeks after trauma. In ears with loss of both short and tall hair cells, little or no functional recovery occurred. In ears with less damage, where significant functional recovery did occur, there were always a few rows of surviving hair cells left at the neural edge of the basilar papilla. In the region of hair cell loss, numerous BrdU labeled cells were found. However, only a small minority of these cells were regenerated hair cells, the majority being monolayer cells. Irrespective of the extent of the region of hair cell loss, regenerated hair cells were observed predominantly in a narrow strip at the transition from the abneural area of total hair cell loss and the neural area of hair cell survival. With increasing damage this strip moved progressively towards the neural edge of the papilla. No regeneration of hair cells was observed in the abneural region of total hair cell loss, even up to 16 weeks after trauma. The results indicate that there is a gradient in the destructive effect of loud sound across the width of the basilar papilla, from most detrimental at the abneural edge to least detrimental at the neural edge. Both tall and short hair cells can regenerate after sound trauma. Whether they do regenerate or not depends on the degree of damage to the area of the papilla where they normally reside. Regeneration of new hair cells occurs only in a narrow longitudinal band, which moves from abneural into the neural direction with increasing damage. In the area neural to this band, hair cells survive the overstimulation. In the area abneural to this band, sound damage is so severe, that no regeneration of hair cells occurs. As a consequence morphological and functional deficits persist.

Acoustic Stimulation↗
PubMed1992

Experimental regeneration in canine muscular dystrophy--1. Immunocytochemical evaluation of dystrophin and beta-spectrin expression.

The expression of dystrophin and beta-spectrin was examined from 1 to 56 days in regenerating muscle fibres in normal and dystrophic dogs, following necrosis induced by the venom of Notechis scutatis. Normal and dystrophic dog muscle regenerated at an equal rate and new myotubes were present in both at the periphery of necrotic fibres by 3 days. In normal dogs dystrophin was detected in the sarcoplasm of the regenerating fibres by 3 days and was localized to the plasma membrane by 4 days. The localization of dystrophin is independent of beta-spectrin and was detected before beta-spectrin, which was not observed until 5-6 days. Normal peripheral labelling of both was restored by 14 days in normal dogs. Normal beta-spectrin labelling of regenerating dystrophic fibres was also restored by 14 days and is not dependent on the presence of dystrophin in dystrophic dogs. A proportion of regenerating fibres in normal and dystrophic dogs showed weak immunolabelling of beta-spectrin prior to 14 days. This is a feature of immature muscle fibres. Antibodies to different domains of dystrophin bound to the periphery and sarcoplasm of regenerating fibres in dystrophic dogs, particularly during the first 7 days of regeneration, but the fluorescence was less intense than in normal dogs. Weak labelling with antibodies corresponding to the C-terminus of the rod domain of dystrophin persisted on dystrophic regenerating fibres up to 21 days. This may relate to developmental isoforms of dystrophin.

Animals↗
PubMed2003

Regeneration of degenerated articular cartilage after high tibial valgus osteotomy for medial compartmental osteoarthritis of the knee.

The aim of the current study was to document regeneration of the articular cartilage after correction of varus deformity for osteoarthritis of the knee. The repair of articular cartilage after high tibial valgus osteotomy for medial compartmental osteoarthritis was observed in 146 knees of 115 patients. The mean age of the patients at osteotomy was 65+/-7 years (range 47-80). Observations were made through an arthrotomy at the time of removal of the blade plate, an average of 2 years after the initial osteotomy. Regeneration of the degenerated cartilage was classified into three stages. There were no regenerative findings (Stage A) in 13 knees; partial regeneration with fibrocartilaginous tissue (Stage B) in the previous degenerated area (Stage B) in 86 knees; and total coverage by new regenerated fibrocartilage or hyaline-like cartilage (Stage C) in 47 knees. Mature regeneration (Stage C) was observed more frequently in the knees with increased width of the medial joint space after high tibial osteotomy than in those with unchanged width (P<0.01), and in the knees with more than 5 degrees of anatomical valgus angulation after osteotomy than in those with less than 5 degrees (P=0.05). Even the knees with eburnation of subchondral bone in the weight-bearing portion showed Stage C regeneration in 26 out of 80, in contrast with no regeneration in two knees with degenerated cartilage remaining. O'Driscoll's histological and histochemical grading score was higher in the Stage C group (P<0.02). The weight-bearing portion of the medial femoral condyle with exposed bone was concluded to be partially or entirely covered by newly regenerated cartilage after 1 year after adequate correction of varus deformity by high tibial osteotomy without antologous chondrocyte implantation.

Aged↗
PubMed2002

Differential changes in protein kinase C associated with regeneration of rat extensor digitorum longus and soleus muscles.

We used a model of crush-induced regeneration in rat in order to characterize biochemically and histologically the implication of protein kinase C (PKC) in muscle repair after damage. In this model, slow soleus and fast extensor digitorum longus (EDL) muscle regeneration proceed differently. PKC activity has been assayed in regenerating muscles and their intact contralateral during the first 14 days following crushing. Degeneration (myolysis) occurring shortly after crush was associated with a marked down-regulation of the enzyme in both wound muscles and notable increase in the corresponding contralateral muscles. Muscle fiber reconstruction in EDL was associated with a rise in PKC activity which peaked at day 7 in regenerating muscle where it was twice higher than in intact muscle. At variance, muscle PKC activity in soleus increased slower than that of EDL and reached later intact level. Western blot analysis and immunohistochemical studies of representative members of the three PKC subfamilies were performed. All the isoform tested were much less expressed in regenerating than in control intact muscles suggesting that the overall PKC activity in regenerating muscles was more activable than in controls. We have shown that PKC isoforms were sequentially expressed during regeneration in both muscle types. PKC theta; being present the earliest, then delta, epsilon and alpha and finally zeta, beta and eta. Some isoforms were differentially expressed according muscle type. PKC delta being more expressed in soleus whereas beta and eta appeared earlier in EDL. Histochemical studies have revealed that the isoforms were differently localized in muscle tissue and that fiber regeneration was associated with PKC alpha translocation from sarcoplasma to sarcolemma. Together these data have shown that multiple PKC isoforms are implicated in the regenerative process acting at different in times and location and suggesting that individual isoform may fulfill distinct functions.

Animals↗
PubMed2003

Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate.

The tail of the frog tadpole, comprising spinal cord, muscle, and notochord, regenerates following partial amputation. We show that, in Xenopus, this occurs throughout development, except for a "refractory period" between stages 45 and 47, when tails heal over without regeneration. Regeneration can be enabled during this refractory period by activation of either the BMP or Notch signaling pathways. Conversely, regeneration can be prevented during the later, regenerative, stages by inhibition of either pathway. BMP signaling will cause regeneration of all tissues, whereas Notch signaling activates regeneration of spinal cord and notochord, but not muscle. An activated form of Msx1 can promote regeneration in the same way as BMP signaling. Epistasis experiments suggest that BMP signaling is upstream of Notch signaling but exerts an independent effect on muscle regeneration. The results demonstrate that regenerative capability can be enabled by genetic modifications that reactivate specific components of the developmental program.

Amputation, Surgical↗
PubMedDate not supplied

The augmenter of liver regeneration induces mitochondrial gene expression in rat liver and enhances oxidative phosphorylation capacity of liver mitochondria.

BACKGROUND: The mammalian augmenter of liver regeneration gene encodes a protein involved in the unique process of liver regeneration. The augmenter of liver regeneration respective protein stimulates hepatocyte proliferation in hepatectomized rats and inhibits cytotoxic activity of liver-derived Natural Killer cells from intact rats. Augmenter of liver regeneration protein shares homology with a Saccharomyces Cerevisiae protein essential for the viability, oxidative phosphorylation and cell-division cycle. AIMS: To demonstrate if augmenter of liver regeneration protein, like the homologous in the yeast, plays a role in the regulation of biogenesis of mitochondria. METHODS: Augmenter of liver regeneration protein was injected in intact rats and, in the hepatic tissue, the expression of two genes located in two different regions of the mitochondrial genome, mitochondrial ATPase 6/8, and ND1 subunit, and of a nuclear gene, mitochondrial Transcription Factor A, were considered. In addition, cytochrome content and oxidative phosphorylation capacity of liver-derived mitochondria were evaluated. RESULTS: The augmenter of liver regeneration protein administration induces an increase in the mitochondrial gene expression and enhances cytochrome content and oxidative phosphorylation capacity of liver-derived mitochondria. CONCLUSIONS: The present data demonstrate a comparable role in the regulation of mitochondria biogenesis in the eukaryotic cell like the yeast protein. This phenomenon could be part of the complex mechanism through which augmenter of liver regeneration regulates hepatocyte proliferation.

Adenosine Triphosphatases↗
PubMedDate not supplied

Axonal regeneration of retinal ganglion cells after optic nerve pre-lesions and attachment of normal or pre-degenerated peripheral nerve grafts.

Axonal regeneration of retinal ganglion cells (RGCs) into a normal or pre-degenerated peripheral nerve graft after an optic nerve pre-lesion was investigated. A pre-lesion performed 1-2 weeks before a second lesion has been shown to enhance axonal regeneration in peripheral nerves (PN) but not in optic nerves (ON) in mammals. The lack of such a beneficial pre-lesion effect may be due to the long delay (1-6 weeks) between the two lesions since RGCs and their axons degenerate rapidly 1-2 weeks following axotomy in adult rodents. The present study examined the effects of the proximal and distal ON pre-lesions with a shortened delay (0-8 days) on axonal regeneration of RGCs through a normal or pre-degenerated PN graft. The ON of adult hamsters was transected intraorbitally at 2 mm (proximal lesion) or intracranially at 7 mm (distal lesion) from the optic disc. The pre-lesioned ON was re-transected at 0.5 mm from the disc after 0, 1, 2, 4, or 8 days and a normal or a pre-degenerated PN graft was attached onto the ocular stump. The number of RGCs regenerating their injured axons into the PN graft was estimated by retrograde labeling with FluoroGold 4 weeks after grafting. The number of regenerating RGCs decreased significantly when the delay-time increased in animals with both the ON pre-lesions (proximal or distal) compared to control animals without an ON pre-lesion. The proximal ON pre-lesion significantly reduced the number of regenerating RGCs after a delay of 8 days in comparison with the distal lesion. However, this adverse effect can be overcome, to some degree, by a pre-degenerated PN graft applied 2, 4, or 8 days after the distal ON pre-lesion enhanced more RGCs to regenerate than the normal PN graft. Thus, in order to obtain the highest number of regenerating RGCs, a pre-degenerated PN should be grafted immediately after an ON lesion.

Animals↗
PubMedDate not supplied

Analysis of dendritic arbors of native and regenerated ganglion cells in the goldfish retina.

The retinas of adult teleost fish can regenerate following injury, but little is known about the neuronal integration of the visual scene that is performed by the regenerated retina. Using goldfish retinal ganglion cells (RGCs) as the experimental system, an evaluation of dendritic arbor structure and passive electrotonic properties was developed, the aim being to quantitatively test the hypothesis that native and regenerated RGC dendritic arbors have similar structural and modeled electrotonic attributes. Fractal dimension was chosen as the descriptor of RGC dendritic arbor complexity, and the arbors' transfer function magnitudes were estimated using an electrically passive, equivalent-circuit analysis. For both native and regenerated RGCs, arbors qualitatively judged to be simple tended to have lower fractal dimension values than arbors judged to be more complex. All cells had similar cut-off frequencies, and for random stimulation of greater than 25% of an RGC's population of dendritic tips, there was a positive correlation between fractal dimension and transfer function magnitude. Some regenerated RGCs had abnormally long primary dendrites, but neither the distributions of fractal dimension values, nor the estimated transfer function magnitudes, were significantly different between native and regenerated RGCs. The results appear to support the hypothesis that structural and modeled electrotonic attributes of regenerated goldfish RGCs are similar to those of native RGCs, suggesting that regenerated RGCs may restore normal visual function.

Affinity Labels↗
PubMed1997

Basic fibroblast growth factor promotes extension of regenerating axons of peripheral nerve. In vivo experiments using a Schwann cell basal lamina tube model.

Schwann cell basal lamina tubes serve as attractive conduits for regeneration of peripheral nerve axons. In the present study, by using basal lamina tubes prepared by in situ freeze-treatment of rat saphenous nerve, the effects of exogenously applied basic fibroblast growth factor (bFGF) on peripheral nerve regeneration was examined 2 and 5 days after bFGF administration. Regenerating axons were observed by light and electron microscopy using PGP9.5-immunohistochemistry for specific staining of axons. In addition, the localizations of bFGF and its receptor (FGF receptor-1) were examined by immunohistochemistry using anti-bFGF antibody and anti-FGF receptor-1 antibody, respectively. Regenerating axons extended further in the bFGF-administered segment than in the bFGF-untreated control segment. Electron microscopy showed that regenerating axons grew out unaccompanied by Schwann cells. Findings concerning angiogenesis and Schwann cell migration were very similar between the bFGF treated and control nerve segment. bFGF-immunoreactivity was not detected in the control nerve segment. In contrast, bFGF-immunoreactivity was detected on the basal lamina tubes as well as on the plasmalemma of regenerating axons facing the basal lamina in the bFGF treated nerve segment up to 5 days after administration, suggesting that exogenous bFGF can be retained in the basal lamina for several days after administration. FGF receptor was detected on the plasma membrane of regenerating axons where they abutted the basal lamina. These results indicate that bFGF could promote the extension of early regenerating axons by directly influencing the axons, but not via Schwann cells or angiogenesis.

Animals↗
PubMed2000

Expression and localisation of IGF-binding protein mRNAs in regenerating rat skeletal muscle.

The expression of the insulin-like growth factor-binding proteins (IGFBP) -3, -4, -5 and -6 was investigated in neonatal, in normal adult and in regenerating rat skeletal muscle. Semi-quantification was done by densitometric scannings of Northern blots. The expression of all investigated IGFBPs, with the exception of IGFBP-5, was higher in neonatal than in adult muscle. During postischaemic regeneration the expression of all IGFBPs increased, but with different time schedules. IGFBP-3 increased transiently during the early phase of regeneration, while IGFBP-4, -5 and -6 increased during the later phase of regeneration. In situ hybridisation on regenerating muscle showed that the expression of the various IGFBPs was cell specific; thus, IGFBP 3 was mainly expressed in macrophages, IGFBP-4 in connective tissue, IGFBP-5 in regenerating muscle cells, and IGFBP-6 in muscle cells, connective tissue and endothelium. Ligand blotting, using 125I-IGF-I as the ligand, showed a number of bands ranging between 24 and 44 kDa. Samples from neonatal and regenerating muscle contained much higher levels of all IGFBPs than those from normal adult muscle. An ordered and cell-specific expression of IGFBPs, allowing a strict regulation of IGF actions, is probably necessary to ensure an optimal regeneration process.

Animals↗
PubMed2000

Early down-regulation of cytochrome P450 3A and 2E1 in the regenerating rat liver is not related to the loss of liver mass or the process of cellular proliferation.

AIMS/BACKGROUND: Conflicting data have been reported concerning the modification of cytochrome P450 expression in the regenerating liver. Ligation of branches of the portal vein (PBL) perfusing 70% of the liver parenchyma, which produces regeneration and atrophy within the same liver, constitutes an ideal model to study the relative specificity of the early events in the regenerating liver and their relationship to the loss of liver mass. METHODS: In this PBL model and in sham models, we studied the expression and the metabolic activities of two major cytochromes, CYP3A and CYP2E1, and the expression of inducible nitric oxide synthase protein (iNOS). They were simultaneously measured in the atrophying and regenerating liver lobes following PBL using Western Blot and HPLC methods. RESULTS: The metabolic activities of both cytochromes were transiently and simultaneously down-regulated in the regenerating and atrophying lobes during the first 2-5 h after PBL. No significant modification was observed at the protein level. In contrast, iNOS protein was significantly induced in both lobes. Similar results were observed after sham operation. CONCLUSIONS: The reduction of these CYP activities in both lobes after PBL and in sham livers suggests that other mechanisms than the regenerating process itself or the reduction of the liver mass might account for such down-regulation during the early phase of liver regeneration. The activation of nitric oxide (NO) and/or pro-inflammatory cytokine production provides clues to pathways liable to affect the CYP activities in the regenerating liver.

Animals↗
PubMedDate not supplied

Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents.

Mammalian myelinated peripheral nerve fibres display a remarkable degree of regeneration following a discrete nerve crush. Nerve crush disrupts the axon cylinder, but leaves the basement membrane of the Schwann cell intact. These intact endoneurial tubes provide pathways to guide the regenerating axon sprouts. After contact with the periphery is established, the regenerating fibres enlarge and myelinate. Conduction velocity recovers to nearly normal and functional recovery is, in many cases, nearly complete. A distinct feature of normal mature myelinated axons is the insensitivity of these fibres to potassium channel blocking agents. In contrast, immature myelinated axons are exquisitely sensitive to the K channel blocking agent 4-aminopyridine (4-AP). Application of 4-AP to immature myelinated fibres leads to a delayed membrane depolarization with action potential burst activity in response to a single stimulus. This sensitivity to 4-AP is attenuated as the fibres mature. Previous studies have demonstrated a sensitivity to 4-AP in regenerating nerve fibres; this sensitivity differentiates the regenerating axon segments from their normal parent axon segments. Such studies have not, however, examined the question of whether regenerated fibres, which have re-established peripheral connections and are functionally active, fully recapitulate the functional organization of normal mature myelinated fibres. We demonstrate here that while sensitivity to the potassium channel blocking agents 4-AP and 3, 4-diaminopyridine (3, 4-DAP) is lost in the normal course of myelinated axon maturation, this property is present in long-term regenerated axons. This suggests that long-term regenerated mammalian axons are characterized by a functional organization that bears a closer resemblance to that of immature myelinated fibres than to that of adult myelinated fibres.

4-Aminopyridine↗
PubMed1999

Re-establishment of visual circuitry after optic nerve regeneration.

In mammals there are a few circumstances in which axotomised ganglion cell axons can regenerate. For instance, in vitro explants of retina can be encouraged to regenerate axons into appropriate culture media. Similarly, axotomised ganglion cells can regenerate into a peripheral nerve graft surgically connected to the optic nerve head, and during early development axons are able to regenerate across the retina to re-enter the optic nerve. This is certainly encouraging, but we are a long way from applying these observations to clinical practice. We need to know whether regenerating axons also retain a functional capacity for navigation. We must ask whether a regenerated projection is likely to be topographic rather than disordered. In this brief review we will look at some selected models of ganglion cell regeneration in order to examine this question of navigation in more detail. This is an important issue: the capacity to re-establish appropriate rather than random connections after ganglion cell regeneration would most likely be necessary for any meaningful return of visual function.

Animals↗
PubMed1999

Fragmenting oligochaete Enchytraeus japonensis: a new material for regeneration study.

Enchytraeus japonensis, a recently described terrestrial oligochaete, reproduces asexually by fragmentation and subsequent regeneration. Taking notice of its high potential as a new material for regeneration study, detailed studies were undertaken on the regeneration and reproduction of E. japonensis. The full-grown body divided into 6-13 fragments that regenerated into complete individuals in 4 days, grew to full length in 10 days, and then fragmented again. Regeneration of the head and tail was epimorphic, involving blastema formation, while old segments in the regenerating fragment morphallactically transformed into the appropriate segments to retain the proper body proportions, which could be visualized by histochemistry for alkaline phosphatase. Artificially cut fragments regenerated either normally or into dicephalic monsters with biaxial heads depending on the conditions. Fragmentation could be induced by decapitation, and sexual reproduction was also found inducible in the laboratory. These findings, together with its simple metameric morphology and ease of culture and handling, suggest that E. japonensis is an excellent material for studying animal regeneration.

Alkaline Phosphatase↗
PubMed2001

Highly efficient transfection system for functional gene analysis in adult amphibian lens regeneration.

The analysis of newt lens regeneration has been an important subject in developmental biology. Recently, it has been reported that the genes involved in the normal eye development are also expressed in the regenerative process of lens regeneration in the adult newt. However, functional analysis of these genes has not been possible, because there is no system to introduce genes efficiently into the cells involved in the regeneration. In the present study, lipofection was used as the method for gene transfer in cultured pigmented iris cells that can transdifferentiate into lens cells in newt lens regeneration. Positive expression of a reporter gene was obtained in more than 70% of cells. In addition, the aggregate derived from gene-transfected cells maintained its expression at a high level for a long time within the host tissue. To verify the effectiveness of this model system with a reporter gene in lens regeneration, Pax6, which is suggested to be involved in normal eye development and lens regeneration, was transfected. Ectopic expression of lens-specific crystallins was obtained in cells that show no such activity in normal lens regeneration. These results made it possible for the first time to analyze the molecular mechanism of lens regeneration in the adult newt.

Animals↗
PubMed2002

Expression of crystallin genes in embryonic and regenerating newt lenses.

The spatio-temporal expression of three crystallin genes (alphaA, betaB1 and gamma) in the developing and regenerating lenses of newt was compared by in situ hybridization in lens differentiation in normal development with during regeneration. In normal development, all crystallin transcripts were first detected at the same stage in the posterior region of the lens vesicle (McDevitt's lens development stage V) and continued during lens fiber differentiation of the posterior cells into the primary lens fiber cell differentiation (McDevitt's lens development stage VII-VIII). At later stages, the expression of the three genes was restricted to the secondary lens fibers and gradually became undetectable in primary lens fibers (McDevitt's lens development stage X). The signal for gamma-crystallin was never detected in lens epithelium at any stage, whereas signals for alphaA- and betaB1-crystallin were detected in the lens epithelium at the stage when the primary lens fiber mass was formed. During lens regeneration, signals for the three crystallins were first detected at the same stage at the ventral margin of a regenerating lens vesicle (Sato's lens regeneration stage IV). The expression patterns of three crystallin genes were similar to those in normal development (Sato's lens regeneration stage V-X). The expression pattern of the crystallin genes in normal lens development fundamentally resembles that during lens regeneration, suggesting the absence of unique expression programs of crystallin genes for lens regeneration not found in ontogeny.

Animals↗
PubMed1980

Ribonucleic acid metabolism during planarian regeneration.

A method for the extraction of total RNA of the planarian Polycelis tenuis is described. This technique has been applied to the study of RNA synthesis in the course of regeneration. Synthesis of RNA begins 7 hrs after sectioning and proceeds in two phases. The first phase, from 7 to 21 hr is characterized by an increased rate of (3H) orotic acid incorporation into RNA up to the 18th after sectioning followed by a decrease between 18 and 21 hrs. The rate of precursor incorporation then had risen again in the second phase to the 30th hr and finally decreased slowly until completion of regeneration. Studies of the pool of nucleotide precursors, show that the observed variations of orotic acid incorporation into RNA reflect variations in RNA synthesis. Electrophoretic analysis of RNA labelled for 2 hrs at various times during regeneration shows that the product formed during the first phase of regeneration is mainly rRNA and low molecular weight RNA. The second phase of the regeneration process, from the 24th hr, is characterized by the appearance of both ribosomal and polydisperse RNAs. These heterogeneous RNA species are detected up to the 46th hr of regeneration, after which time rRNA again becomes predominent. The significance of the two phases of RNA metabolism of which this is the first observation during planarian regeneration is discussed in connection with other biochemical events which have been described during regeneration processes in planarians and other animals.

Animals↗
PubMed2004

Negative regulation of liver regeneration by innate immunity (natural killer cells/interferon-gamma).

BACKGROUND AND AIMS: Hepatic lymphocytes are composed mainly of natural killer (NK) cells and NKT cells, which play key roles in innate immune responses against pathogens and tumors in the liver. This report analyzes the effects of activation of innate immunity by viral infection or the toll-like receptor 3 (TLR3) ligand on liver regeneration. METHODS: The partial hepatectomy (PHx) method was used as a model of liver regeneration. Murine cytomegalovirus (MCMV) infection and the TLR3 ligand polyinosinic-polycytidylic acid [poly(I:C)] were used to activate innate immunity. RESULTS: NK cells are activated after PHx, as evidenced by producing interferon (IFN)-gamma. Infection with MCMV or injection of poly(I:C) further activates NK cells to produce IFN-gamma and attenuates liver regeneration in the PHx model. Depletion of NK cells or disruption of either the IFN-gamma gene or the IFN-gamma receptor gene enhances liver regeneration and partially abolishes the negative effects of MCMV and polyI:C on liver regeneration, whereas NKT cells may only play a minor role in suppression of liver regeneration. Adoptive transfer of IFN-gamma +/+ NK cells, but not IFN-gamma -/- NK cells, restores the ability of polyI:C to attenuate liver regeneration in NK-depleted mice. Finally, administration of polyI:C or IFN-gamma enhances expression of several antiproliferative proteins, including STAT1, IRF-1, and p21cip1/waf1 in the livers of partially hepatectomized mice. CONCLUSIONS: Our findings suggest that viral infection and the TLR3 ligand negatively regulate liver regeneration via activation of innate immunity (NK/IFN-gamma), which may play an important role in the pathogenesis of viral hepatitis.

Adoptive Transfer↗