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Results for “Extracellular Matrix”

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PubMed1992

Production of extracellular matrix by glomerular epithelial cells is regulated by transforming growth factor-beta 1.

Transforming growth factor-beta (TGF-beta) has widespread effects on extracellular matrix production by many cultured cell lines and appears to play a role in the pathological accumulation of extracellular matrix that accompanies inflammatory and fibrotic diseases such as glomerulonephritis. Earlier experiments have shown that mesangial cells respond to TGF-beta 1 with a marked increase in the production of two chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, but their production of other matrix components elevated in glomerulonephritis is not substantially affected by TGF-beta 1. Since the glomerular epithelial cells are also thought to contribute to matrix production in the glomerulus, we examined the ability of these cells to produce some of the nonproteoglycan matrix components in response to TGF-beta 1. Exposure of glomerular epithelial cells to TGF-beta 1 increased the production of fibronectin and type IV collagen, in addition to biglycan. Enhancement of the cell layer accumulation of laminin was also observed. These results show that TGF-beta 1 has a differential effect on extracellular matrix production by epithelial and mesangial cells from glomeruli. TGF-beta 1 released in the glomerulus secondary to injury could thus affect both cell types and lead to increased intraglomerular production of proteoglycans, whereas the increased fibronectin, type IV collagen, and laminin may primarily originate from the epithelial cells.

Animals↗

PubMed2002

Monocyte-macrophage differentiation in vitro: modulation by extracellular matrix protein substratum.

The influence of extracellular matrix (ECM) on monocyte-macrophage (mo-mphi) differentiation was investigated using an in vitro model with human peripheral blood mononuclear cells (PBMC) maintained on different matrix protein substrata. Macrophage specific markers associated with differentiation studied were, (a) endocytosis of modified proteins; (b) appearance of mphi specific matrix metalloproteinases (MMPs); (c) activities of myeloperoxidase (MPO) and beta-D-glucuronidase; (d) changes in the expression of cell surface antigens. As the duration of monocytes in culture increased, a progressive increase in the rate of differentiation was seen as evidenced by mphi specific functions such as endocytosis of 125[I] acetyl BSA and the appearance of gelatinases A and B. Significantly higher rate of endocytosis and production of MMPs were found in monocytes maintained on fibronectin (FN) and COL I than on COL IV (FN > COL I > COL IV) indicating that cells in contact with stromal components differentiate at a faster rate. FACS analysis done on cells maintained in vitro for phenotypic profile characteristic to mo-mphi differentiation showed downregulation of CD14 occurring in a substratum dependent manner viz, (FN > COL IV > COL I) and upregulation of CD71 was high in cells maintained on COL I and COL IV. Intracellular enzymatic activities such as MPO significantly decreased irrespective of matrix substrata, while beta-D-glucuronidase activity increased in a substratum dependent manner (FN > COL I > COL IV). Pretreatment of cells with genistein significantly decreased the secretion of MMPs, particularly MMP 9 in cells maintained on ECM protein (FN) indicating a phosphorylation dependent signalling process in mediating matrix effect. The results of these in vitro studies on mphi specific markers suggest that apart from the diffusible factors, the microenvironment as provided by various matrix proteins particularly FN can modulate mo-mphi differentiation.

Antigens, Surface↗

PubMed2000

Control of extracellular matrix assembly by syndecan-2 proteoglycan.

Extracellular matrix (ECM) deposition and organization is maintained by transmembrane signaling and integrins play major roles. We now show that a second transmembrane component, syndecan-2 heparan sulfate proteoglycan, is pivotal in matrix assembly. Chinese Hamster Ovary (CHO) cells were stably transfected with full length (S2) or truncated syndecan-2 lacking the C-terminal 14 amino acids of the cytoplasmic domain (S2deltaS). No differences in the amount of matrix assembly were noted with S2 cells, but those expressing S2deltaS could not assemble laminin or fibronectin into a fibrillar matrix. The loss of matrix formation was not caused by a failure to synthesize or externalize ECM components as determined by metabolic labeling or due to differences in surface expression of alpha5 or beta1 integrin. The matrix assembly defect was at the cell surface, since S2deltaS cells also lost the ability to rearrange laminin or fibronectin substrates into fibrils and to bind exogenous fibronectin. Transfection of activated alphaIIbalphaLdeltabeta3 integrin into alpha(5)-deficient CHO B2 cells resulted in reestablishment of the previously lost fibronectin matrix. However, cotransfection of this cell line with S2deltaS could override the presence of activated integrins. These results suggest a regulatory role for syndecan-2 in matrix assembly, along with previously suggested roles for activated integrins.

Amino Acid Sequence↗

PubMed1994

Integral proteins of the extracellular matrix fibrils of Myxococcus xanthus.

The extracellular matrix fibrils of Myxococcus xanthus are mediators of cell-cell cohesion and as such are required for the maintenance of the social lifestyle characteristic of these prokaryotes. The fibrils have also been implicated as factors involved in contact-mediated cell interactions and in signal exchange. The fibrils are extracellular carbohydrate structures with associated proteins. All of the major proteins associated with the fibrils react with monoclonal antibody 2105 and can be removed from the fibrils only by boiling with sodium dodecyl sulfate (SDS) and beta-mercaptoethanol. For consistency with their integral association with the fibrils, we have designated this class of proteins as integral fibrillar proteins class 1 (IFP-1). IFP-1 comprises five major proteins whose molecular sizes range from 66 to 14 kDa. All of the proteins in IFP-1 have been purified from isolated fibrils by electroelution after size separation on SDS-PAGE gels. Analysis of the purified proteins suggested that the forms with different molecular sizes result from the aggregation of a single small-molecular-size subunit. Fingerprint analysis and amino acid composition profiles confirmed the identity among the different members of IFP-1. The sequence of the 31 amino-terminal amino acids of the 31-kDa form of IFP-1 (IFP-1:31) was determined. There was no significant homology to other known protein sequences. During development there is a dramatic shift in the banding pattern of IFP-1 proteins without any apparent overall loss of total protein.

Amino Acid Sequence↗

PubMed1987

Binding of heparin to human endothelial cell monolayer and extracellular matrix in culture.

Endothelial binding of heparin contributes to its local antithrombotic action and catabolism. However, it is uncertain whether heparin may be bound to a damaged or even de-endothelialized vessel surface. Therefore, the binding of 3H-heparin to cultured endothelial cell monolayer and extracellular matrix was studied. The binding reached equilibrium after 4 h. 3H-heparin bound to endothelium could be displaced by unlabelled heparin which competed for about 80% of binding. The binding became saturable when the concentration of heparin exceeded 30-times the therapeutical value. Approximately 6 X 10(11) binding sites for heparin per cm2 of endothelium were calculated. Heparin was bound not only to endothelial cells but also to extracellular matrix, even when it was exposed in the absence of cells. About 40% of binding sites were localized in the extracellular matrix fraction. A similar affinity of binding of 3H-heparin to complete endothelium, endothelial cells and extracellular matrix was estimated /Kd of almost 1 microM/. The binding of heparin to extracellular matrix should be considered in the interpretation of heparin interaction with endothelium.

Cells, Cultured↗

PubMed1995

Regulation of mesenchymal extracellular matrix protein synthesis by transforming growth factor-beta and glucocorticoids in tumor stroma.

We have here studied the composition and regulation of stromal extracellular matrix components in an experimental tumor model. Nude mice were inoculated with WCCS-1 cells, a human Wilms' tumor cell line. In the formed tumors the stroma was found to contain mesenchymal extracellular matrix proteins such as tenascin-C, fibulins-1 and 2 and fibronectin, but no nidogen. Nidogen was confined to basement membranes of tumor blood vessels. Since glucocorticoids have been shown to downregulate tenascin-C expression in vitro, we tested whether dexamethasone can influence biosynthesis of extracellular matrix components during tumor formation in vivo. A downregulation of tenascin-C mRNA and an upregulation of fibronectin mRNA expression by dexamethasone was noted. Transforming growth factor-beta 1 mRNA levels were unaffected by the dexamethasone treatment. Glucocorticoids can thus downregulate tenascin-C synthesis although local stimulatory growth factors are present. The competition between a negative and a positive extrinsic factor on synthesis of stromal extracellular matrix components was studied in a fibroblast/preadipocyte cell line. Transforming growth factor-beta 1 stimulated tenascin-C synthesis but did not affect fibronectin or fibulin-2 synthesis. Dexamethasone at high concentrations could completely suppress the effect of transforming growth factor-beta 1 on tenascin-C mRNA expression. Transforming growth factor-beta 1 could in turn overcome the downregulation of tenascin-C mRNA expression caused by a lower concentration of dexamethasone. We therefore suggest that the limited expression of tenascin-C in part is due to a continuous suppression by physiological levels of glucocorticoids, which can be overcome by local stimulatory growth factors when present in sufficient amounts.

Animals↗

PubMed1983

Fibronectin-independent adhesion of fibroblasts to extracellular matrix material: partial characterization of the matrix components.

Fibroblasts can adhere to extracellular matrix (ECM) material by fibronectin-dependent (type I) and fibronectin-independent (type II) mechanisms. In this report we investigate the biochemical characteristics of ECM that contribute to type II adhesion. ECM capable of mediating type II adhesions is produced primarily by normal diploid fibroblasts, but not by transformed cells or epithelial cells. Treatment of fibroblast ECM under conditions that result in the removal of most of the ECM lipid or most of the ECM glycosaminoglycan does not impair type II adhesion. Likewise, treatment of the ECM with large amounts of purified collagenase does not block type II adhesion. However, treatment of ECM with low doses of trypsin or with an agent that reacts with tyrosine residues, results in complete ablation of the ability of the ECM to support type II adhesion. On the basis of these observations we suggest that the matrix component(s) mediating type II adhesion are non-collagenous proteins or glycoproteins.

Animals↗

PubMed2026

Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.

The extracellular matrix (ECM) is a dynamic structural network that supports tissue architecture and regulates cell function. It is primarily composed of collagens, elastin, proteoglycans, and glycoproteins, which are synthesized by canonical and non-canonical ECM-producing cells. During aging, the ECM undergoes progressive changes in structure and composition, a process recently recognized as the 13th hallmark of aging. In skeletal muscle (SKM), age-associated ECM remodeling, largely regulated by immune system-ECM crosstalk, contributes to sarcopenia and impaired regeneration. Macrophages (MΦs), as key innate immune cells, regulate ECM dynamics both indirectly by activating canonical ECM-producing cells and directly by synthesizing ECM components. Notably, a distinct subset of ECM-producing MΦs that express collagen (COL+ MΦs) has been identified across multiple tissues, although their function in SKM homeostasis and aging remains poorly understood. Here, we review current knowledge of ECM production and remodeling, with special emphasis on MΦ involvement, including COL+ MΦs, as critical regulators of fibrogenesis, especially during SKM aging and regeneration.

Extracellular Matrix↗

PubMed1991

Synthesis of extracellular matrix by macrophage-modulated retinal pigment epithelium.

In proliferative vitreoretinopathy, macrophages and retinal pigment epithelial cells are associated with microfibrillar matrix proteins in the vitreous cavity, but the contribution of this extracellular matrix to the pathophysiology is not known. We used radiolabeling techniques on cultured human retinal pigment epithelial cells to correlate the secretion of extracellular matrix proteins with macrophage-induced modulation of cell proliferation and morphologic features. Retinal pigment epithelial cells incubated in a macrophage-conditioned medium assumed fibrocytelike morphologic characteristics, grew faster, and exhibited a decreased cellular release of fibrillar and nonfibrillar matrix components. However, due to a simultaneous greater increase in cell numbers in these modulated cultures, the total production of fibrillar and nonfibrillar matrix components by the culture population was increased.

Cell Division↗

PubMed1992

Effects of TGF beta 1 on the proliferation and differentiation of an immortalized astrocyte cell line: relationship with extracellular matrix.

The astrocyte cell line (C.LT.T.1.1.), which is immortalized and has retained a normal density-dependent regulation of growth, is a suitable model for studying the relationships between proliferation, differentiation, and the production of extracellular matrix. The growth factor TGF beta 1 was used to modulate these processes. When added to proliferative cells, it inhibited growth and caused morphological changes. It also suppressed the growth arrest at confluence, so that the cells formed multilayers of parallel spindle-shaped cells. Whereas untreated control cells expressed progressively the glial fibrillary acidic protein (GFAP) after arrest of multiplication, the addition of TGF beta 1 to proliferative cells prevented GFAP expression and accumulation of its mRNA. Concomitantly, it increased the amounts of laminin, fibronectin, and collagens synthesized during the growth phase and greatly altered the composition and the structure of the matrix deposited at confluence. In contrast, when added after cell differentiation had begun, TGF beta 1 did not alter the appearance of the matrix whereas it still stimulated, but to a lesser extent, extracellular matrix components production. The results show that TGF beta 1 prevents the transition from the proliferating to the differentiating state and correlatively alters the composition and structure of the extracellular matrix.

Animals↗

PubMed2005

The effect of irradiation and hyperbaric oxygenation (HBO) on extracellular matrix of the condylar cartilage after mandibular distraction osteogenesis in the rabbit.

The effects of irradiation and hyperbaric oxygenation (HBO) on the extracellular matrix of condylar cartilage after mandibular distraction were evaluated. Unilateral distraction was performed on 19 rabbits. Five study groups were included: control, low- and high-dose irradiation, and low- and high-dose irradiation groups with HBO. Additionally, four temporomandibular joints (TMJ) were used as control material. The high-dose irradiated animals were given in the TMJ 22.4 Gy/4 fractions irradiation (equivalent to 50 Gy/25 fractions). Low-dose irradiation group received a 2.2 Gy dosage. Two groups were also given preoperatively HBO 18 x 2.5ATA x 90 min. After a two-week distraction period (14 mm lengthening) and four-week consolidation period the TMJs were removed. Proteoglycan (PG) distribution of the extracellular matrix was evaluated using safranin O staining and collagen I and II using immunohistochemistry. The organization of fibrillar network was studied by polarized light microscopy. On the operated side of the control group and on the unoperated side in all, except for high-dose irradiated group, PG distribution and fibrillar network were normal appearing. In the irradiated groups, with or without HBO, the cartilaginous layer was partially or totally devoid of PG and the network structure was severely damaged. In conclusion, irradiation in conjunction with the pressure applied by distraction causes severe damage to extracellular matrix of condylar cartilage.

Animals↗

PubMed1988

Extracellular matrix triggers a directed cell migratory response in sea urchin primary mesenchyme cells.

The role of extracellular matrix in cell migration has generally been considered in terms of a substratum. However, when thin cell processes from migrating sea urchin primary mesenchyme cells contact small latex beads coated with extracellular matrix from the blastocoel, the cells migrate directly to the coated beads. Since the beads are not anchored, this result indicates that highly localized contact with the extracellular matrix can stimulate movement independently of any change in cell adhesion.

Animals↗

PubMed1999

Effect of HMG-CoA reductase inhibitors on extracellular matrix expression in human vascular smooth muscle cells.

Clinical studies have shown that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can stabilize atherosclerotic plaques and slow their progression. One determinant of plaque stability and size is the composition of the vascular extracellular matrix. The aim of this study was to evaluate the effects of different HMG-CoA reductase inhibitors on the expression of major components of the vascular extracellular matrix in smooth muscle cells. Cultured human vascular smooth muscle cells were incubated for 24-72 h with the HMG-CoA reductase inhibitors lovastatin (1-50 micromol/L), simvastatin (0.05-20 micromol/L), and pravastatin (1-100 micromol/L). RNA expression of the extracellular matrix proteins thrombospondin-1, fibronectin, collagen type I, and biglycan as well as expression of the cytokine TGF-beta1 was determined by Northern blotting. Extracellular matrix protein secretion was visualized by immunofluorescence. In addition, cell proliferation and viability were measured using BrDU-ELISAs, MTT-tests, and direct cell counting. Expression of thrombospondin-1 was significantly decreased after 24 h incubations with lovastatin in concentrations as low as 1 micromol/L. Coincubation with the cholesterol precursor mevalonate completely reversed this effect. The downregulation of thrombospondin-1 expression occured in the same concentration range that also inhibited cell proliferation. In contrast, lovastatin did not affect expression of fibronectin, whereas collagen type I and biglycan expression decreased only after long incubations with high, toxic lovastatin concentrations. Simvastatin, but not the very hydrophilic compound pravastatin, had a similar effect on extracellular matrix expression as lovastatin. In summary, lovastatin and simvastatin predominantly decrease the expression of the glycoprotein thrombospondin-1, which is functionally associated with smooth muscle cell migration and proliferation. In contrast, expression of plaque-stabilizing extracellular proteins such as collagen type I and biglycan are much less affected.

Cell Division↗

PubMed1992

Modulation of 5'-nucleotidase activity in plasma membranes and intact cells by the extracellular matrix proteins laminin and fibronectin.

Modulation of 5'-nucleotidase activity by the extracellular matrix proteins fibronectin, laminin and their fragments has been studied in plasma membrane preparations as well as in intact BCS-TC2 and Rugli cells. The ectoenzyme on plasma membranes is activated by laminin; fibronectin inhibits the AMPase activity on BCS-TC2 plasma membranes but no inhibitory effect is found in plasma membrane preparations from Rugli cells. These effects are dependent on the preincubation time and protein concentration. When the effect of the extracellular matrix proteins is studied on intact cells, both BCS-TC2 and Rugli cells show similar behaviour. A decrease in the enzyme activity is observed in the presence of fibronectin. The AMPase inhibitory activity is located on its 40 kDa fragment. No inhibitory activity is found in other fibronectin fragments, including the 140 kDa fragment which contains the RGDS cell-adhesion sequence. Laminin and its E1-4 and E8 fragments are able to activate the ecto-5'-nucleotidase activity of both BCS-TC2 and Rugli cells. The effect of the E1-4 fragment on intact cells is greater than that observed for the E8 fragment and uncleaved laminin. Our results suggest a bifunctional role for 5'-nucleotidase as ectoenzyme and cell receptor for extracellular matrix proteins.

5'-Nucleotidase↗

PubMed1990

Plasminogen-activator inhibitor type 1 is a potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinoma cells.

We have analyzed the role of plasminogen-activator inhibitor type 1 (PAI-1) in the regulation of tumor cell-mediated extracellular matrix degradation. Immunocytochemical analysis revealed PAI-1 associated with microgranular and fibrillar material of the extracellular matrix and demonstrated the presence of PAI-1 as a cell surface-associated antigen. Transforming growth factor beta significantly reduced matrix degradation mediated by HT-1080 human fibrosarcoma cells. This inhibition was correlated with an increase in PAI-1 antigen expression, whereas urinary-type plasminogen activator (u-PA) secretion was unaffected. In this experimental system, PAI-1 regulated extracellular matrix breakdown, as added PAI-1 inhibited matrix solubilization, whereas monoclonal antibodies to PAI-1 increased it. A cell line (LPAI) producing high levels of biologically active PAI-1 was established by transfection of a human PAI-1 cDNA clone into mouse L cells. Coculture experiments demonstrated that LPAI cells prevented matrix degradation by Lu-PA cells (L cells expressing high levels of u-PA) or Co-115 human colon carcinoma cells (expressing tissue-type plasminogen activator). These results indicate that PAI-1 may play a critical role in the regulation of extracellular matrix degradation during tumor cell invasion.

Animals↗

PubMed1996

Tissue origin and extracellular matrix control neutral proteinase activity in human fibroblast three-dimensional cultures.

Remodeling of the extracellular matrix by fibroblasts is an important step in the process of wound healing and tissue repair. We compared the behavior of fibroblasts from two different tissues, dermis and gingiva, in three-dimensional lattices made of two different extracellular matrix macromolecules, collagen and fibrin. Cells were grown in monolayer cultures from normal skin or gingiva and seeded in three-dimensional lattices made of either collagen of fibrin. Photonic and scanning electron microscopy did not reveal any morphological differences between the two types of fibroblasts in both sets of lattices. Both types of fibroblasts retracted collagen lattices similarly and caused only a slight degradation of the collagen substratum. By contrast, when seeded in fibrin lattices, gingival fibroblasts completely digested their substratum in less than 8 days, whereas only a slight fibrin degradation was observed with dermal fibroblasts. The ability of gingival but not dermal fibroblasts to express high levels of tissue plasminogen activators (tPA) when cultured in fibrin lattices was assessed on an immunological basis. Also, deprivation of plasminogen-contaminating fibrinogen preparations or use of tPA inhibitors markedly inhibited both fibrinolysis and retraction rates of fibrin lattices by gingival fibroblasts. Casein-zymography confirmed the intense proteolytic activity induced by fibrin in gingival fibroblasts. It was inhibited by aprotinin and phenyl methylsulfonyl fluoride (PMSF), two non-specific inhibitors of serine proteinases, and by epsilon-amino-caproic acid (epsilon ACA), an inhibitor of plasminogen activators. Monolayer cultures exhibited only trace amounts of caseinolytic activity. Our results demonstrate that the expression of proteinases by fibroblasts is dependent not only on their tissue origin but also on the surrounding extracellular matrix. The intense fibrinolytic activity of gingival fibroblasts in fibrin lattices may explain partially the high rate of healing clinically observed in gingiva.

Adult↗

PubMed1998

Effects of soluble factors and extracellular matrix on DNA synthesis and surfactant gene expression in primary cultures of rat alveolar type II cells.

Proliferation and differentiation of epithelial cells are thought to be regulated by soluble factors in extracellular fluid and insoluble components of the extracellular matrix. We have examined the combined effects of soluble factors and an extracellular matrix (EHS matrix) on DNA synthesis, cell proliferation, and surfactant protein gene expression in primary cultures of alveolar type II epithelial cells. Cells on EHS matrix cultured in DMEM containing insulin, cholera toxin, EGF, aFGF, 5% rat serum, and 15-fold concentrated bronchoalveolar lavage fluid (D-GM) formed larger aggregates than cells cultured on the same substratum in DMEM containing 5% rat serum (D-5). Cells cultured in D-GM on EHS matrix incorporated more [3H]-thymidine than cells on the same substratum in D-5, with an eight-fold increase seen on day 4 of culture. This increase in [3H]-thymidine incorporation was accompanied by a labeling index of greater than 65% of the cells. Cell counts showed that exposure of type II cells on EHS matrix to D-GM resulted in increased cell number on day 4 of culture. [3H]-thymidine autoradiography combined with immunostaining with anti-cytokeratin, anti-SP-A, and anti-vimentin antibodies demonstrated that the proliferating cells were epithelial cells that contained SP-A. Type II cells cultured on plastic in D-GM also showed increased [3H]-thymidine incorporation compared to cells cultured in D-5. The level of [3H]-thymidine incorporation by cells on plastic, however, was significantly less than that seen in cells cultured in the same medium on EHS matrix. Type II cells cultured on EHS matrix in D-GM had a decreased abundance of mRNAs for SP-A and SP-C than cells cultured on EHS matrix in D-5 as determined by Northern analysis. This inhibition was reversed by switching from D-GM to D-5 on day 4 and culturing the cells for an additional 4 days. In contrast, SP-B mRNA was increased in response to D-GM. This increase was not reversed by switching from D-GM to D-5 on day 4. These results suggest that the interaction of soluble factors and extracellular matrix components has a strong influence on type II cell proliferation, which were partially associated with the reversible inhibition of lung tissue-specific protein mRNAs. Their dynamic interplay among the type II cell, the extracellular matrix, and growth factors may determine multicellular functions and play an important role in normal lung development and in the repair of the lung epithelium following injury.

Animals↗

PubMed2005

TNFalpha-mediated extracellular matrix remodeling is required for multiple division cycles in rat hepatocytes.

During liver regeneration, hepatocytes proliferate under the control of both proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and growth factors, in parallel to extracellular matrix remodeling. This study investigated mechanisms by which mitogen and extracellular matrix signals are linked for inducing proliferation of differentiated hepatocytes. The authors used adult rat hepatocytes in coculture with liver biliary cells, because cells are stably differentiated for several weeks, capable of extracellular matrix deposition, and unable to divide in response to growth factor alone. This work demonstrated that hepatocytes could undergo several proliferation waves without loss of differentiation by using alternating periods of TNFalpha/growth factor stimulation and deprivation. Three days after stimulation with TNFalpha and epidermal growth factor (EGF), up to 35% of hepatocytes divided. Demonstration was also provided that EGF alone only promoted cell progression up to late G(1), whereas TNFalpha was necessary for G(1)/S transition and Cdk1 induction. TNFalpha promoted an extracellular matrix (ECM) degradation that involved the matrix metalloproteinase MMP-9 induction through activation of NF-kappaB pathway. Finally, the authors showed that ECM remodeling signal was required for initiating any new hepatocyte division wave, in presence of mitogen. In conclusion, these results highlight that hepatocyte division is dependent on ECM deposition associated with differentiation status, and that ECM degradation signal is critical in controlling G(1)/S transition and Cdk1 induction. These results provide new insights for understanding the unique hepatocyte proliferation control and improving regeneration in patients suffering from liver damage.

Animals↗