scholarly journals Understanding the Role of Gui-Zhi-Fu-Ling-Capsules (Chinese Medicine) for Treatment of Endometriosis in the Rat Model: Using NMR Based Metabolomics

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jue Zhou ◽  
Zhi-Ming Ding ◽  
Paul J. Hardiman
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Serum Levels ◽  
Normal Group ◽  
Sham Operation ◽  
Group Model ◽  
Model Group ◽  
Expression Levels ◽  
Glut 4 ◽  
Mrna Expression Levels

The objective of this study is to identify the changes of metabolites in the rat endometriosis models treated with Gui-Zhi-Fu-Ling-capsules (GZFLC), a classic Chinese medicinal formula, and to explore the effects of GZFLC on the serum levels of transforming growth factor-β1 (TGF-β1) and the mRNA expression levels of vascular endothelial growth factor (VEGF) and glucose transporter 4 (GLUT-4) in the endometriotic tissues. Forty female Wistar rats were randomly divided into the sham-operation group (Normal group), Model group, Danazol group, and GZFLC group. The serum levels of TGF-β1 were measured using enzyme-linked immune-sorbent assay (ELISA). The mRNA expression levels of VEGF and GLUT-4 in the endometriotic tissue of the rat endometriosis models were measured using real-time quantitative PCR. The metabolites in urine were detected by 1H NMR method. Eight identified metabolites of the NMR resonance were involved in the glycolysis metabolism. Among the 8 metabolites, Lactate, Acetate, TMA, and Formate were downregulated with GZFLC. Citrate, TMAO, Taurine, and Hippurate were unregulated with GZFLC. The serum levels of TGF-β1 in the Danazol and GZFLC groups were significantly higher than those of Normal group and significantly lower than the Model group. GZFLC treatment significantly decreased the GLUT-4 and VEGF mRNA expression levels in the endometriotic tissues of the endometriosis rats (P < 0.05). GZFLC significantly decreased the GLUT-4 mRNA expression levels in rats of GZFLC group compared with Danazol group. It is through regulating the metabolites changes of glycolysis or gluconeogenesis that GZFLC significantly affected the expression levels of TGF-β1, GLUT-4, and VEGF of the model rats with endometriosis.

scholarly journals Loss of sphingosine 1-phosphate receptor 3 gene function impairs injury-induced stromal angiogenesis in mouse cornea

2020 ◽  
Author(s):  
Shingo Yasuda ◽  
Takayoshi Sumioka ◽  
Hiroki Iwanishi ◽  
Yuka Okada ◽  
Masayasu Miyajima ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Vascular Endothelial ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Expression Levels ◽  
Sphingosine 1 Phosphate ◽  
Mrna Expression Levels

AbstractSphingosine 1-phosphate (S1P) is a bioactive sphingolipid generated through sphingosine kinase1 (SPK1)-mediated phosphorylation of sphingosine. We show here that injury-induced S1P upregulation increases corneal neovascularization through stimulating S1PR3, a cognate receptor. since this response was suppressed in S1PR3-knockout mice. Furthermore, Cayman10444, a selective S1PR3 inhibitor, reduced this response in WT mice. Such reductions in neovascularization were associated with reduced vascular endothelial growth factor A (VEGF-A) mRNA expression levels in WT TKE2 corneal epithelial cells and macrophages treated with CAY10444 as well as macrophages isolated from S1PR3 KO mice. S1P increased tube-like vessel formation in human vascular endothelial cells (HUVEC) and human retinal microvascular endothelial cells (HRMECs) cells expressing S1PR3. In S1PR3 KO mice, TGFβ1-induced increases in αSMA gene expression levels were suppressed relative to those in the WT counterparts. In S1PR3 deficient macrophages, VEGF-A expression levels were lower than in WT macrophages. Transforming growth factor β1(TGFβ1) upregulated SPK1 expression levels in ocular fibroblasts and TKE2 corneal epithelial cells. CAY10444 blocked S1P-induced increases in VEGF-A mRNA expression levels in TKE2 corneal epithelial cells. Endogenous S1P signaling upregulated VEGF-A and VE-cadherin mRNA expression levels in HUVEC. Unlike in TKE2 cells, SIS3 failed to block TGFβ1-induced VEGF-A upregulation in ocular fibroblasts. Taken together, these results indicate that injury-induced TGFβ1 upregulation increases S1P generation through increases in SPK1 activity. The rise in S1P formation stimulates the S1PR3-linked signaling pathway, which in turn increases VEGF-A expression levels and angiogenesis in mouse corneas.

scholarly journals Zika virus infection during pregnancy and induced brain pathology in beclin1-deficient mouse model

2019 ◽  
Author(s):  
Mohan Kumar Muthu Karuppan ◽  
Chet Raj Ojha ◽  
Myosotys Rodriguez ◽  
Jessica Lapierre ◽  
M. Javad Aman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mouse Model ◽  
Mrna Expression ◽  
Zika Virus ◽  
Neuronal Injury ◽  
Viral Rna ◽  
Expression Levels ◽  
Inflammatory Molecules ◽  
Mrna Expression Levels

ABSTRACTWe investigated the role of the autophagy protein, Beclin1, in the replication and disease of Zika virus (ZIKV) in pregnant dams and their offspring using Beclin1-deficient (Atg6+/−) and wild-type (Atg6+/+) mouse model infected with the Honduran (R103451), Puerto Rican (PRVABC59), and the Uganda (MR766) strains of ZIKV. Pregnant dams infected subcutaneously at embryonic stage (E)9 showed viral RNA in serum harvested at E13 and in various organs removed postmortem at E17. Subcutaneous infections with ZIKV also showed the vertical transmission of ZIKV from the placenta to embryos removed postmortem at E17. From the three isolates, R103451-infected Atg6+/− dams had the lowest mortality rate while 30 % of their offspring containing the hemizygous beclin1 allele (Atg6+/−) were smaller in size and had smaller and underdeveloped brain. Growth impairment in the pups became noticeable after two weeks post-birth. After 21-days, pups were sacrificed and brain tissues removed postmortem showed expression of the envelope (E) and the non-structural (NS)-1 proteins, along with signs of neuronal injury, despite an absence in viral RNA detection. A significant decrease in the mRNA expression levels of the insulin-like growth factor-1 (IGF-1) by 8-fold and a decrease in the mRNA expression levels of several microcephaly related genes along with an increase in the secretion of several inflammatory molecules may have contributed to the observed phenotype. Since autophagy regulates cytokines and chemokines production, a dysregulation in this pathway may have further exacerbated the pathology of ZIKV.IMPORTANCEPups delivered from ZIKV-infected dams showed significant growth impairments in the body and the brain. We believe that the reduction in insulin growth factor together with the increase secretion of inflammatory molecules may have triggered neuronal injury and the downregulation of the microcephalic genes, while reduced expression of the autophagy protein, Beclin1 further exacerbated the pathology. Although the mechanism is still unknown, the autophagy pathway seems to play a key role in ZIKV pathology. It is therefore of great significance to study the role of autophagy during viral infection with the goal to identify potential targets for anti-ZIKV therapeutic intervention.

scholarly journals Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Reproduction ◽  
2015 ◽  
Vol 149 (6) ◽  
pp. 645-655 ◽  
Author(s):  
Oscar E Rivera ◽  
Jorgelina Varayoud ◽  
Horacio A Rodríguez ◽  
Clarisa G Santamaría ◽  
Verónica L Bosquiazzo ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mrna Expression ◽  
Estrogen Receptor Alpha ◽  
Ovarian Function ◽  
Steroid Receptors ◽  
Ovarian Response ◽  
Serum Levels ◽  
Lower Number ◽  
Expression Levels ◽  
Mrna Expression Levels

Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 μg/kg per day, BPA0.5: 0.5 μg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17β-estradiol (E2), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles ≥2 mm in diameter together with a lower number of atretic follicles and no increase in E2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood.

scholarly journals The expression and prognostic value of the epidermal growth factor receptor family in glioma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Xu ◽  
Zhengyuan Huo ◽  
Hui Huang ◽  
Wei Ji ◽  
Zheng Bian ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Expression ◽  
Growth Factor Receptor ◽  
Who Grade ◽  
Expression Levels ◽  
Epidermal Growth ◽  
Egfr Family ◽  
Mrna Expression Levels

Abstract Background The epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of the tyrosine kinase I subfamily and has 4 members: EGFR/ERBB1, ERBB2, ERBB3, and ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers. Materials/methods In this study, we used multiple online bioinformatics websites, including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID, to study the expression profiles, prognostic values and immune infiltration correlations of the EGFR family in glioma. Results We found that EGFR and ERBB2 mRNA expression levels were higher in glioblastoma (GBM, WHO IV) than in other grades (WHO grade II & III), while the ERBB3 and ERBB4 mRNA expression levels were the opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were upregulated, which was associated with a poor prognosis. In addition, correlation analysis between EGFR family expression levels and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. The PPI network of the EGFR family in glioma and enrichment analysis showed that the EGFR family and its interactors mainly participated in the regulation of cell motility, involving integrin receptors and Rho family GTPases. Conclusions In summary, the results of this study indicate that the EGFR family members may become potential therapeutic targets and new prognostic markers for glioma.

scholarly journals Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma

2020 ◽  
Author(s):  
Muhammad Shahidan Muhammad Sakri ◽  
Wan Faiziah Wan Abdul Rahman ◽  
Tengku Ahmad Damitri Al-Astani Tengku Din ◽  
Hasnan Jaafar ◽  
Vinod Gopalan
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Breast Carcinoma ◽  
Mrna Expression ◽  
Platelet Factor 4 ◽  
Vascular Endothelial ◽  
Platelet Factor ◽  
Expression Levels ◽  
Endothelial Growth Factor ◽  
Mrna Expression Levels

AbstractAngiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1, and Flt-4, have been found to play an essential role in regulating angiogenesis. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4, and rapamycin+platelet factor-4. The tumors were subsequently subjected to immunohistological protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semi-quantitative scoring method, while the mRNA expression levels were analyzed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4 treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent anti-angiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

scholarly journals The Expression and Prognostic Values of Epidermal Growth Factor Receptor Family in Glioma

2021 ◽  
Author(s):  
bin xu ◽  
wei ji ◽  
zhengyuan huo ◽  
zheng bian ◽  
jiantong jiao ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Expression ◽  
Growth Factor Receptor ◽  
Who Grade ◽  
Expression Levels ◽  
Epidermal Growth ◽  
Egfr Family ◽  
Mrna Expression Levels

Abstract Background: Epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of tyrosine kinase I subfamily, including 4 members, they are EGFR/ERBB1, ERBB2, ERBB3, ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers.Material/Methods: In this research, we used multiple online bioinformatics websites including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID to study the expression profiles, prognostic values and immune infiltration correlations of EGFR family in glioma.Results: We found that EGFR and ERBB2 mRNA expression levels were the higher in glioblastoma (GBM, WHO IV) than other grades (WHO grade II&III), While ERBB3 and ERBB4 mRNA expression levels were opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were the opposite. Besides, ERBB2 and ERBB4 in glioma patients were associated with poor prognosis. In addition, correlation analysis between EGFR family expression and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. PPI network of EGFR family in glioma and enrichment analysis showed that EGFR family and their interactors mainly participated in regulation of cell motility involved integrin receptors and Rho family GTPases.Conclusions: In summary, this study indicates that EGFR family may become potential targets and new prognostic markers for glioma.

scholarly journals The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age

2015 ◽  
Vol 26 (15) ◽  
pp. 2733-2741 ◽  
Author(s):  
Flaviana Marzano ◽  
Annamaria Ventura ◽  
Mariano Francesco Caratozzolo ◽  
Italia Aiello ◽  
Francesca Mastropasqua ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Mrna Expression ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Insulin Like Growth Factor ◽  
Proliferating Cells ◽  
P53 Family ◽  
Expression Levels ◽  
Mrna Expression Levels

The regulation of insulin-like growth factor–binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood.

scholarly journals Reproductive Hormones and Their Receptors May Affect Lung Cancer

2017 ◽  
Vol 44 (4) ◽  
pp. 1425-1434 ◽  
Author(s):  
Mengmeng Dou ◽  
Keyan Zhu ◽  
Zhirui Fan ◽  
Yuxuan Zhang ◽  
Xiufang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mrna Expression ◽  
Serum Levels ◽  
Tumour Volume ◽  
Reproductive Hormones ◽  
Control Group ◽  
Expression Levels ◽  
Tumour Weight ◽  
Subcutaneous Inoculation ◽  
Mrna Expression Levels

Background/Aims: In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. Methods: Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ERα (oestrogen receptor α) and ERβ (oestrogen receptor β) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ERα and ERβ were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. Results: Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83±0.40 and 3.13±0.43, P<0.05). E2 and T serum levels decreased exponentially in the ovariectomized group, while the E2/T ratio increased compared with the control group (E2: 55.88±11.45 and 78.21±9.37; T: 0.82±0.14 and 1.46±0.16; ratio: 69.62±14.43±29.81 and 52.22±5.42; all P<0.05). The Western blot and IHC results indicated that AR, ERα and ERβ protein expression levels were obviously higher in transplanted tumour and lung tissues from the ovariectomized group, with particular increases in ERβ in transplanted tumour tissue and in ERα in lung tissue. The PCR results also showed markedly higher mRNA expression levels of AR, ERα and ERβ in the ovariectomized group, and in particular, ERβ in transplanted tumour tissue and ERα in lung tissue were significantly increased in the ovariectomized group. Conclusion: Ovariectomy decreased E2 and T serum levels and increased the E2/T ratio in mice, and this imbalance in the internal environment promoted the growth of transplanted tumours. Sex hormone disorder not only promoted transplanted tumour growth but also significantly reduced the protein and mRNA expression levels of sex hormone receptors. The metabolism of E2 and T may affect the growth, proliferation and metabolism of lung cancer cells, and the mechanism by which sex hormones and their receptors influence lung cancer is worthy of further research.

scholarly journals High-trans fatty acid and high-sugar diets can cause mice with non-alcoholic steatohepatitis with liver fibrosis and potential pathogenesis

2020 ◽  
Author(s):  
Xin Xin ◽  
Bei-yu Cai ◽  
Cheng Chen ◽  
Hua-jie Tian ◽  
Xin Wang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Model Group ◽  
Expression Levels ◽  
Alcoholic Steatohepatitis ◽  
Tgf Β1 ◽  
Mrna Expression Levels ◽  
Liver Tissues

Abstract Aims To establish a mouse model of non-alcoholic steatohepatitis (NASH) within liver fibrosis using a high-fat and high-carbohydrate diet (HFHC) and to analyze potential pathogenesis using a transcriptome microarray. Methods Sixty mice were stratified by weight and randomly divided into HFHC model and control (Con) groups, with 30 mice in each group. Both HFHC and Con mice were euthanized at 0, 20 and 30 weeks. The following analyses were performed: biochemical analysis; histological assessment; Col-I, α-SMA and TGF-β1 protein and mRNA expression levels; and transcriptomic gene chip analysis. Results Compared with the Con group at each time point, the body weight and liver wet weight of the HFHC model group mice were significantly higher. At 30 weeks, ALT, AST, FBG and FINS levels or activities and TG and HYP contents in the HFHC model group were significantly elevated. Severe steatosis was present in the liver tissues from HFHC group mice. Substantial perisinusoidal fibrosis with a cage-like structure and bridging formations were observed in the liver. Col-I, α-SMA and TGF-β1 protein and mRNA expression levels in liver tissues from HFHC mice increased over time. Compared with the Con group, the HFHC group had 151 differentially expressed genes that were involved in 41 signaling pathways. Conclusions After 30 weeks of a HFHC diet, the mice exhibited substantial liver fibrosis, hepatic steatosis, ballooning degeneration and inflammation. The formation of an experimental NASH combined with liver fibrosis mouse model may be related to ECM-receptor interaction, Toll-like receptor signaling and other signaling pathways.

scholarly journals High-trans fatty acid and high-sugar diets can cause mice with non-alcoholic steatohepatitis with liver fibrosis and potential pathogenesis

2020 ◽  
Author(s):  
Xin Xin ◽  
Bei-yu Cai ◽  
Cheng Chen ◽  
Hua-jie Tian ◽  
Xin Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Fibrosis ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Model Group ◽  
Expression Levels ◽  
Alcoholic Steatohepatitis ◽  
Tgf Β1 ◽  
Mrna Expression Levels ◽  
Liver Tissues

Abstract Background and Aims: Even Non-alcoholic steatohepatitis (NASH) has been becoming the key role in process of liver fibrosis or cirrhosis, no any NASH involving liver fibrosis mice model which consistent with the mechanisms of fatty acid and glucose metabolism disorder was widely accepted. Here, we established a mouse model of nonalcoholic steatohepatitis (NASH) with liver fibrosis using a high-fat, high-carbohydrate diet (HFHC) and analyzed the potential pathogenesis using a transcriptome microarray. Methods: Fifty mice were stratified by weight and randomly divided into the HFHC model and control (Con) groups. 10 mice were sacrificed at the beginning of the experiments, 10 mice of HFHC and Con group were euthanized at the end of 20 and 30weeks. The following analyses were performed: biochemical analysis; histological assessment; evaluation of hepatic type I collagen (Col-I), α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) protein and mRNA expression levels; and transcriptomic gene chip analysis. Results: Compared with the Con group at each time point, the body weight and liver wet weight of the HFHC model group of mice were significantly higher. At 30th weeks, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG) and fasting insulin (FINS) levels or activities and the triglyceride (TG) and hydroxyproline (HYP) content in the HFHC model group were significantly elevated. Severe steatosis was present in the liver tissues contributed from the HFHC group of mice. Typically, substantial perisinusoidal fibrosis with a cage-like structure and bridging formations were observed in the mice liver in HFHC group. Col-I, α-SMA and TGF-β1 protein and mRNA expression levels in liver tissues of HFHC mice dramatically increased over time. Compared with the Con group, the HFHC group had 151 differentially expressed genes that were involved in 41 signaling pathways. Conclusions: After keeping 30 weeks HFHC diet treatment, the mice exhibited substantial liver fibrosis, hepatic steatosis, ballooning degeneration and inflammation. Basing on the transcriptome microarray assays, the experimental NASH involving liver fibrosis potentially related to dramatically changed ECM-receptor interaction, Toll-like receptor signaling and other signaling pathways.

Sign in / Sign up

Export Citation Format

Share Document