Maximal inflammation was more than twice as extensive Palbociclib purchase in the OPN-deficient mandibles as in the WT tissues.

The pro-inflammatory molecules known as IL-1 (comprising both IL-1α and IL-1β) are responsible for much of the pathology in these periapical infections25 and can mediate osteoclast activation and function.26 We used qPCR to evaluate the effect of OPN deficiency on IL-1 expression in the periapical lesions. Interleukin-1α, but not IL-1β, was significantly increased in lesions from OPN-deficient mice compared with WT mice at early times after infection (Fig. 3a). Consistent with the increased bone loss seen in these animals, RANKL expression was also increased in OPN-deficient mice. By 21 days, however, there were no significant differences in the expression of these cytokines between the two genotypes (Fig. 3b). The number of osteoclasts was greatly elevated in the periapical region of infected mice at 3 days after infection, as compared with control, unexposed animals. However, the number of osteoclasts in these areas was not different between WT and OPN-deficient animals (Fig. 3c). This is consistent with the similar extent learn more of bone loss in the WT and OPN-deficient mice at this time-point.

Together these results suggest that OPN acts to enhance the bone loss seen at later times, which reflects the increased bone resorption between 3 and 21 days after infection. Osteopontin has been associated with the Th1 response, which is known to exacerbate inflammation-associated bone loss in our endodontic infection model.27 It can also suppress the expression of IL-10,9 which has an anti-inflammatory role

in these infections.28 To assess the effect of OPN on the Th1/Th2 response in these infections, the serological response of infected animals to bacterial infection was determined 3 weeks after infection. Levels of IgG1 and IgG2a, were determined Doxacurium chloride in sera from infected mice by ELISA using F. nucleatum as antigen: this species has been shown previously to elicit a strong immune response.7 The ratio of the expression of these isoforms reflects the Th1/Th2 balance, such that IGg2a ≥ IgG1 indicates a Th1 bias, whereas lower IgG2a suggests a Th2 polarization.24,29 In WT mice, the humoral immune response to this species included both IgG1 and IgG2a, although the titre of IgG2a was somewhat higher, perhaps reflecting a Th1 bias. There were no significant changes in either IgG1 or IgG2a levels in the absence of OPN (Fig. 4a), suggesting that there is no alteration in the Th1/Th2 polarization in these lesions in the absence of OPN. This idea is supported by analysis of messenger RNA (mRNA) levels for a series of cytokines in the periapical lesions at 21 days after infection. While OPN has been reported to enhance IL-12 expression and suppress IL-10,9 IL-12, IL-10 and IFN-γ mRNA levels were similar in both WT and OPN-deficient mice (Fig. 4b).

The next day, wells were sequentially incubated with 200 μL blocking buffer (PBS solution, 0.5% Tween 20, 4% dry milk, 10% fetal bovine serum), 100 μL specimen (serum 1 : 50 or stool 1 : 10 in blocking buffer) and 100 μL of horseradish peroxidase goat anti-mouse (Zymed–Invitrogen, San Francisco, CA) immunoglobulin G (IgG) (1 : 4000) or IgA (1 : 2000) in blocking buffer. Incubations were performed for 1 h at room temperature and plates were washed with PBS–Tween 20 (0.05%) between steps. A reaction was developed with 100 μL tetramethylbenzidine substrate (Sigma-Aldrich) for 10 min, stopped with MK-8669 cell line 100 μL 1 N H2SO4 and the absorbance was determined at a wavelength of 450 nm. All of the specimens were tested

in duplicates and the background reading of noninoculated wells was subtracted selleck chemicals from test wells. Four weeks after the third dose of immunization, animals were challenged with H. pylori. For that, H. pylori SS1 strain (kindly provided by Dr R.M. Peek, Vanderbilt University, Nashville, TN) was grown at 37 °C in brucella broth (Becton Dickinson & Co., Sparks, MD) with 10% fetal bovine serum and antibiotics (vancomycin 10 μg mL−1 and amphotericin B 5 μg mL−1) under microaerophilic conditions (GasPak EZ, Becton Dickinson & Co.) and a suspension of 1–5 × 109 bacteria in PBS administered by gastric gavage every other day for three doses. Four weeks after the challenge, mice were

euthanized and the stomach was harvested to determine the presence of H. pylori organisms. Stomachs were homogenized (Tissue Tearor, Biospec Products, Bartlesville, OK), DNA was extracted (Dneasy Tissue Kit, Qiagen) and subjected to quantitative real-time PCR (Béguéet al., 2006) using primers described previously by Roussel et al. (2007) and targeted to the H. pylori SS1 16S rRNA gene (411–564 bp). Specimens were run in duplicates and positive and negative controls (H. pylori-infected and -uninfected mice, respectively)

were included. In addition, to confirm that the detected signal was due to H. pylori in the specimens, the 16S rRNA gene was amplified (69–611 bp) by regular PCR using primers described by Thoreson et al. (1995), and the resulting amplicon was sequenced at Louisiana State University Health Sciences Center Genomics Core Facility and compared with the H. GNA12 pylori SS1 16S rRNA gene (GenBank AY366421). Difference in antibody and H. pylori infection levels between groups were compared using the nonparametric Mann–Whitney U-test (spss 14.0; SPSS, Chicago, IL). The animal experimentation protocol was reviewed, approved and supervised by the Institutional Animal Care and Use Committee of the Research Institute for Children, Children’s Hospital, New Orleans, LA. The results of immunogenicity are shown in Fig. 1. Figure 1a shows serum anti-urease B IgG antibodies. As noted, intranasal administration of rUreB was poorly immunogenic, despite the use of CpG ODN as an adjuvant, and not different from the control group.

aureus, followed by various Gram-negative organisms, including B. cepacia complex and Serratia marcescens. Recurrent impetigo, frequently in the perinasal area and caused by see more S. aureus, usually requires prolonged courses of oral and topical antibiotics to clear. Hepatic (and perihepatic) abscesses are also quite common in CGD and are caused typically by S. aureus. Patients usually present with fever, malaise and weight loss. Osteomyelitis is another important infection in CGD and can arise from haematogenous spread of organisms

(S. aureus, Salmonella spp., S. marcescens) or contiguous invasion of bone, seen typically with non-A. fumigatus pneumonia, such as A. nidulans spreading to the ribs or vertebral bodies. Perirectal abscesses are also common in CGD patients, and once formed can persist for years despite aggressive anti-microbial therapy and fastidious local care. Other frequently encountered catalase-positive microbial agents are Escherichia coli species, Listeria species, Klebsiella species, Nocardia and Candida species. CGD patients usually manifest their symptoms at an early age, in the first 2 years of life. However, due to the diverse genetic causes of the disease (see below), some patients may also present later in life. Most CGD patients (about 80%) are male, because the main cause of the disease is a mutation in an X-chromosome-linked learn more gene. However, defects in autosomal genes may also underlie the disease and cause

CGD in both males and females. CGD is caused by the failure of the patients’ phagocytic leucocytes to kill a wide variety of pathogens. This is due to a defect in these phagocytes in producing reactive oxygen species (ROS), which are needed for the killing process. In normal phagocytes, these ROS are generated by an enzyme called

nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This enzyme is composed of five subunits, two of which are in resting cells localized in the plasma membrane and three in the cytosol. The two membrane-bound subunits are a transmembrane glycoprotein (gp) with a molecular mass of 91 kD, called gp91phox (phox for phagocyte oxidase) and another transmembrane protein with a molecular mass of 22 kD, called p22phox. These Protirelin two proteins form a heterodimer and are dependent upon each other’s presence for maturation and stable expression. This heterodimer is called cytochrome b558 because gp91phox contains two haem groups with an absorbance peak at 558 nm. The three cytosolic subunits (p40phox, p47phox and p67phox) form a heterotrimer that translocates to cytochrome b558 upon cell activation (e.g. by binding of micro-organisms or chemotactic factors to membrane receptors). As a result, the conformation of gp91phox is slightly changed, which enables NADPH in the cytosol to bind and donate electrons to this protein. These electrons are then transported within gp91phox to molecular oxygen on the apical side of the membrane.

“
“Aim:  Only few studies have reported that betel nut (BN) chewing is independently associated

with chronic kidney disease (CKD); however, the sample size was relatively small. This study was to explore further the association between BN chewing and CKD using a larger case series. Methods:  We retrospectively reviewed the records of a health check-up program from 2003 to 2009. Laboratory tests, medical history and status of cigarette smoking, alcohol drinking and BN chewing were compared between CKD and non-CKD groups. We checked interaction effects between BN chewing and all other covariates, and conducted multivariate logistic regression analysis to explore the risk AP24534 of CKD with BN chewing. Results:  A total of 27 482 participants (15 491 females and 11 991 males, mean age 58.02 ± 11.85 years) were included in the study, of whom 4519 (16.4%) had CKD and 1608 (5.9%) chewed BN. CKD prevalence in the chewers was higher than in the non-chewers in all age find more groups per decade. BN chewing was significantly associated with CKD in overall subjects (odds ratio (OR) = 1.23, P = 0.027) and also in the male (OR = 1.23, P = 0.035), non-drinking (OR = 1.62, P = 0.000), non-diabetic (OR = 1.27, P = 0.021), and non-proteinuric groups (OR = 1.30, P = 0.013). This relationship was insignificant in female, drinking, diabetic and proteinuric groups. Conclusion: 

The association between BN chewing and CKD seemed conditional on demographics, health behaviours, and underlying co-morbidities. This association should be interpreted cautiously. “
“Aim:  Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribute to the development of tubulointerstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). The aim of this study was to investigate the therapeutic effect of MMP inhibitor, Terminal deoxynucleotidyl transferase doxycycline, administration in an experimental rat model of immune-complex nephritis (ICN). Methods:  The induction of immune-complex glomerulonephritis

was carried out by the administration of an i.v. dose of 2 mg bovine serum albumin (BSA) daily for 28 days after 8 weeks of s.c. immunization with 1 mg of BSA in complete Freund’s adjuvant. Doxycycline (30 mg/kg) was given daily (in groups 2 and 4) by gavage for 28 days. Results:  Animals treated with doxycycline showed significant reduction in glomerular area and cell proliferation than non-treated controls. Glomerular deposition of immunoglobulin (Ig)G and C3 was less intense in treated rats than non-treated controls. Although not statistically significant, interstitial inflammation was less intense in treated rats than non-treated controls. Glomerular expression of MMP-9 by immunoflourescence was significantly inhibited in the treated group. In addition pro-MMP-2 on gelatin zymography was importantly suppressed by doxycycline in ICN.

One of the striking observations in the IL-17/IL-22 axis in

our experimental model of DENV-2 infection is the fact that infected IL-22−/− mice presented increased production of IL-17A in the spleen and liver, and neutralization of IL-17A in these mice reverted the worsened phenotype observed in mice lacking IL-22. Other studies have addressed the cross-talk between IL-17A and IL-22 production. Besnard et al.[132] showed that IL-22 may regulate the expression and pro-inflammatory properties of IL-17A in allergic lung inflammation. Sonnenberg et al.[112] described that IL-17A could suppress IL-22 expression in Th17 cells after bleomycin-induced lung inflammation and fibrosis. Although a Idasanutlin molecular weight reciprocal regulation LDK378 in vitro of IL-17A and IL-22 is observed in vivo, the underlying cellular and molecular mechanisms that may affect the functional properties of these cytokines in distinct peripheral tissues are yet to be described. Therefore, IL-22 seems to counterbalance the

production of IL-17A in experimental severe dengue infection. Pro-inflammatory mediators produced by epithelial cells in response to IL-17A are neutrophil- and granulocyte-attracting chemokines (i.e. CXCL1, CXCL2), IL-6 and several growth factors.[13-15] Neutrophil accumulation and activation are increased in DENV infection, so this could be an important function for IL-17A in this disease. In addition, IL-17A expression is markedly reduced in the spleens of iNKT-cell-deficient mice (Jα18−/−) during infection (R. Guabiraba, J. Renneson, and F. Trottein, unpublished data). The close association of iNKT TGF-beta inhibitor cells and the production of IL-17 or IL-22 in experimental DENV infection might require further investigation. Although thrombocytopenia is observed

in mild and severe forms of DENV infection, the role of platelet activation in dengue pathogenesis has not been fully elucidated. Hottz et al.[133] hypothesize that platelets have major roles in inflammatory amplification and increased vascular permeability during severe forms of dengue. They reported an increased expression of IL-1β in platelets and platelet-derived microparticles from patients with dengue or after platelet exposure to dengue virus in vitro. Further, DENV infection led to microparticle release through mechanisms dependent on NLRP3 inflammasome activation and caspase-1-dependent IL-1β secretion by platelets. Inflammasome activation and platelet shedding of IL-1β-rich microparticles correlated with signs of increased vascular permeability. Moreover, microparticles from DENV-stimulated platelets induced enhanced permeability in vitro in an IL-1-dependent manner.

43) for fin whales only. Mixing models were rerun where sprat and herring age classes were pooled but correlations between source posterior

distributions were greater (< −0.50), providing justification for the stratification of fish isotopic data by age. In Bayesian inference, given data (D) and a model (M) the probability from the posterior distribution is presented as Pr(D|M). Assuming that the model includes all major diet sources, both fin and humpback whale diets included large proportions Selleckchem Ku 0059436 of fish. Krill comprised a greater proportion of the diet of fin whales than in humpback whales (Pr(D|M) = 0.979). For fin whales, krill species were collectively the most dominant (maximum a posteriori probability estimate, low–high 95% credibility intervals) diet component (0.46, 0.22–0.59). Both fin and humpback whales were found to have a preference for age 0 sprat (0.22, 0.00–0.37 and 0.30, 0.01–0.38, respectively) and herring (0.17, 0.01–0.35 and 0.22, 0.02–0.36, respectively) (Fig. 4). The probability that krill comprised a greater proportion than the next most abundant component (age 0 sprat) was 0.996 (Fig. 3, 4). While there was a high probability that age 0 sprat were more abundant in fin whale diet solution than either age 1 (0.696) or age 2 (0.786), the probability that sprat was greater

see more than herring when posterior age class distributions were pooled was very low, Pr(D|M) = 0.318 (Fig. 3, 4). Krill exhibited a wide range in δ13C which is consistent with a high degree of spatio-temporal variability within the sample (Fig. 2). Despite this, however, the mixing model solutions show unambiguous isotopic

separation between fish and krill, leading to reduced uncertainty when partitioning diet sources (Fig. 3). A prior assessment of likely diet components of fin and humpback whales in the CS was made, based on the best available evidence from the literature and field observations. This guided the selection of sources CYTH4 for the isotope mixing model. A caveat of this approach was that sources used in the mixing models were unlikely to be an exhaustive representation of the species diversity in the diet of fin and humpback whales which may feed on other fishes, e.g., anchovy (Engraulis encrasicolus), pilchard (Sardina pilchardus), mackerel or blue whiting (Micromesistius poutassou), or indeed other species of zooplankton, e.g., Calanus spp. or Thysanoessa spp. However, there was no evidence from the literature, or from field observations indicating that these species are preyed upon by fin and humpback whales in the CS or contiguous waters. While a sufficient sample size was obtained for fin whales (n = 21), it should be noted that results for humpback whales are based on a small sample (n = 4) and should therefore be interpreted with caution. A potential source of bias in our results is the differential tissue turnover rate between krill and fish muscle.

65 (p = 0.018), and platelet count lower than 105,500/mm3 (p = 0.02). Platelet count lower than 105,500/mm3 had the highest discriminative value for presence of large EV (sensitivity = 73.33%; specificity = 73.33%; area under receiver operating characteristics = 0.783). Conclusions: Large EV were found in 66.7% of patients with liver cirrhosis who underwent hospitalization. In patients with liver cirrhosis, the existence of thrombocytopenia may predict large EV which warrant prophylactic therapy. Keyword(s): 1. large esophageal varices; 2. liver cirrhosis; 3. platelets Presenting Author: FEI KONG www.selleckchem.com/products/CP-673451.html Additional Authors: JING JIANG, MS JIN, HX MA, JQ NIU Corresponding Author:

XUEYUAN CAO Affiliations: NVP-BGJ398 First Hospital of Jilin University, First Hospital of Jilin University, First Hospital of Jilin University, First Hospital of Jilin University Objective: Galectins (Gal) are multifunctional galectins binding

to the β-galactoside of glycoproteins that affect diverse physiological and pathophysiological processes. Previous studies have reported a correlation between galectin expressions and neoplastic transformation, progression and prognosis. The objective of this study was to evaluate the role of the expression of Gal-3 and Gal-9 in hepatocellular carcinoma (HCC) and their prognostic values. Methods: Gal-3 and Gal-9 expression was evaluated in 247 HCC patients using tissue microarray immunohistochemistry method, of which 110 had paired adjacent normal samples. Correlations were analyzed between expression levels of Gal-3 and Gal-9 protein and tumor parameters or clinical outcomes. Results: Gal-3 expression was ADAMTS5 found in 52 of 110 tumor tissues, significant higher than that in adjacent hepatic tissues (47.3% vs 18.2%, P < 0.001), while no significant differences was observed in expression of Gal-9 (P = 0.430). Gal-3 expression was statistically correlated with histological differentiation (P = 0.016) and lymph-vascular invasion (P = 0.049) and cirrhosis (P = 0.040). Gal-9 expression was also correlated with histological differentiation (P = 0.002) and lymph-vascular invasion (P = 0.012).

Kaplan-Meier analysis showed that patients with higher Gal-3 expression had worse overall survival (P = 0.008), however, no relationship was found in Gal-9 expression and survival (P = 0.150). Multivariate analysis showed that multiple tumor (RR = 2.97, 95%CI = 1.39–6.33, P = 0.005), lymph-vascular invasion (RR = 2.80, 95%CI = 1.14–6.93, P = 0.025) and Gal-3 expression (RR = 2.24, 95%CI = 1.29–3.89, P = 0.004) were independent factors of prognosis in HCC. Conclusion: Gal-3 expression was involved in tumor progression and related to the prognosis of HCC, while Gal-9 expression was only related to tumor progression. Gal-3 is expected to serve as a novel diagnostic and prognostic marker of HCC. Key Word(s): 1. hepatocellular carcinoma; 2. galectin-3; 3. galectin-9; 4.

To sustain and build upon WFH success, we must also cultivate and integrate these youth into the work of the WFH and NMOs. The first 3 years of the WFH strategic plan focused on building our global family to include more fully those with VWD, rare factor deficiencies and inherited platelet disorders. The WFH is now looking to expand our youth

programmes to ensure that LDE225 order a future generation is ready to assume the mantle of leadership [46]. Additionally, through enhanced youth education, awareness and engagement, we will assure continuity within WFH NMOs, build greater unity among our global family and perhaps most importantly capture their innovative and creative ideas to help realize our vision of Treatment for All. World Federation of Hemophilia programmes are evolving to incorporate an integrated approach to youth leadership development with supplementary components such as youth specific publications,

youth opportunities in WFH development programmes such as twinning, utilization of social media forums such as Facebook and Twitter [47], expanded youth fellowship programmes and a summer camp programme ‘Journey Around the World’ (JAW) [48]. JAW is an innovative game for children and youth attending summer camps to raise their awareness of the needs of people with haemophilia in developing Cyclooxygenase (COX) countries. JAW engages youth in more developed countries to give back to the global community, as well as recognize the importance of continued advocacy to sustain PD0325901 their own care. We are now working across the spectrum to establish a

wide range of programmes and opportunities for youth leadership and involvement. Although this article has selected three specific segments of our global family for visibility and emphasis, it should not be concluded that these are the only ones with challenges or deserving of attention. The particular emphasis placed on women, children and youth, and those in sub-Saharan Africa is due to their critical importance and previously lagging visibility relative to other segments and regions. To fully achieve our vision of Treatment for All, we must learn from our experiences, build upon all of our many successes, embrace the diversity of bleeding disorders and construct a future where all patients regardless of who they are or where they might live realize the hope and promise of Treatment for All. The WFH gratefully acknowledges the support of so many for their commitment and dedication – the national member organizations, WFH volunteers and staff, the healthcare professionals and governments committed to building national care programmes and the WFH’s partners and donors that provide financial support.

Gaining a better understanding of how CD8+ T cells are activated in the liver, and in particular in chronic viral hepatitis, will give us more insight

into how to better generate effective therapies. We thank Dr. K. Reed Clarke for the preparation of the AAV vectors. “
“Abnormalities of gastrointestinal (GI) motor function contribute to a number of common clinical problems seen by gastroenterologists. Proper evaluation of patients with suspected functional gastrointestinal disorders and gastrointestinal motility disorders is important for correct diagnosis and an appropriate plan of treatment. This chapter discusses motility tests assessing esophageal, gastric, small intestinal, colonic, and anorectal function. The GI motility laboratory serves as an important station for patient evaluation and treatment

in gastroenterology. “
“The overall survival AZD3965 of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of αB-Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies αB-Crystallin Inhibitor Library expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of αB-Crystallin promotes HCC progression in Silibinin vivo and in vitro. We demonstrate that αB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells

through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. αB-Crystallin complexes with and elevates 14-3-3ζ protein, leading to up-regulation of ERK1/2 activity. Moreover, overexpression of αB-Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra-1/slug signaling pathway. Clinically, our data reveal that overexpression of both αB-Crystallin and 14-3-3ζ correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with αB-Crystallin overexpression. Conclusion: These data suggest that the αB-Crystallin-14-3-3ζ complex acts synergistically to promote HCC progression by constitutively activating ERK signaling. This study reveals αB-Crystallin as a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response. (HEPATOLOGY 2013) Hepatocellular carcinoma (HCC) is one of the major health problems worldwide.1 Because HCC is often diagnosed at an advanced stage, a large proportion of HCC patients display symptoms of intrahepatic metastases or postsurgical recurrence at the time of diagnosis. HCC is among the leading causes of cancer-related deaths in Asia, especially in China.

However, such molecules should be related to viral

persistence and should be good candidates in the development of new therapies against HCV. The classification of HCV genotypes has been established, and genotype determination has become easier with recent improvements in nucleotide sequencing technology. A new genotype may potentially be found in areas where medical supplies are insufficient. Genetic variability of the virus affects liver cell metabolism and influences the outcome of IFN therapy. Further precise analysis of nucleotide and amino acid sequences of the virus and association with human genome polymorphisms will give us the opportunity to better understand phenomena caused by host and virus interactions. https://www.selleckchem.com/products/azd4547.html This work was supported in part by Grants-in-Aid for scientific research and development from the Ministry of Health, Labor and Welfare and Ministry of Education, Culture Sports Science and Technology, Government of Japan. We thank Dr Keiko Arataki of Hiroshima Memorial Hospital and Sakura Akamatsu for their assistance. “
“The origin of fibrogenic cells in liver fibrosis remains controversial. We assessed the emerging concept that hepatocytes contribute to production RG7422 solubility dmso of extracellular matrix (ECM) in liver fibrosis through epithelial-mesenchymal transition (EMT). We bred triple transgenic

mice expressing ROSA26 stop β-galactosidase (β-gal), albumin Cre, and collagen α1(I) green fluorescent protein (GFP), in which hepatocyte-derived cells are permanently labeled by β-gal and type I collagen-expressing

cells are labeled by GFP. We induced liver fibrosis by repetitive carbon tetrachloride (CCl4) injections. Liver sections and isolated cells were evaluated for GFP and β-gal as well as expression of α-smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1). Upon stimulation with transforming growth factor β-1, cultured hepatocytes isolated from untreated liver expressed both GFP and β-gal with a fibroblast-like morphological Neratinib change but lacked expression of other mesenchymal markers. Cells from CCl4-treated livers never showed double-positivity for GFP and β-gal. All β-gal-positive cells exhibited abundant cytoplasm, a typical morphology of hepatocytes, and expressed none of the mesenchymal markers including α-SMA, FSP-1, desmin, and vimentin. In liver sections of CCl4-treated mice, GFP-positive areas were coincident with fibrotic septa and never overlapped X-gal-positive areas. Conclusion: Type I collagen-producing cells do not originate from hepatocytes. Hepatocytes in vivo neither acquire mesenchymal marker expression nor exhibit a morphological change clearly distinguishable from normal hepatocytes. Our results strongly challenge the concept that hepatocytes in vivo acquire a mesenchymal phenotype through EMT to produce the ECM in liver fibrosis. (HEPATOLOGY 2009.