4.Transforming Growth Factor-beta 1 Involved in the Pathogenesis of Endometriosis through Regulating Expression of Vascular Endothelial Growth Factor under Hypoxia.
Yue-Xin YU ; Yin-Ling XIU ; Xi CHEN ; Ya-Li LI
Chinese Medical Journal 2017;130(8):950-956
BACKGROUNDEndometriosis (EMs) is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. Transforming growth factor-beta 1 (TGF-β1) plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions.
METHODSEndometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA (mRNA) and protein expression levels of TGF-β1, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) were measured. A Dual-Luciferase Reporter Assay was used to examine the effect of TGF-β1 and hypoxia on a VEGF promoter construct. Student's t-test was performed for comparison among groups (one-sided or two-sided) and a value of P < 0.05 was considered statistically significant.
RESULTSTGF-β1, VEGF, HIF-1α mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue (t = 2.16, P = 0.042). EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein (t = 6.84, P = 0.023). VEGF mRNA levels increased 12.5% in response to TGF-β, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production (87.5% increases) of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 (2.6-fold, t = 6.08, P = 0.032) or hypoxia (11.2-fold, t = 32.70, P < 0.001), whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect (18.5-fold, t = 33.50, P < 0.001).
CONCLUSIONSThe data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-β1 and hypoxia is taking place at the transcriptional level.
Blotting, Western ; Cells, Cultured ; Endometriosis ; genetics ; metabolism ; Female ; Humans ; Hypoxia ; genetics ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Transforming Growth Factor beta ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism
5.Dynamic changes of TGF-α and TGF-β1 in rats with liver cirrhosis induced by multiple pathogenic factors.
Xiao-xia TIAN ; Hui-ying ZHANG ; Li-min WANG ; Xu-jiong LI ; Yan LIU ; Li-li ZHANG ; Yang-hui BI
Chinese Journal of Applied Physiology 2016;32(1):65-68
OBJECTIVETo explore the dynamic changes of transforming growth factor-α (TGF-α) and transforming growth factor-β1 (TGF-β1) of liver cirrhosis induced by multiple pathogenic factors in rats.
METHODSAnimals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride (CCl₄), the CCl₄(0.5 ml/100 g · w) was injected at the first day of experiment and the 40% CCl₄oil solution (0.3 ml /100 g · w) was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8 th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase (ALT), endotoxin, tumor necrosis factor-α (TNF-α) and homocysteine (Hcy) in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-α and TGF-β1 were analyzed by the method of immunohistochemistry.
RESULTSCompared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-α and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4th, 6th and 8th week (P < 0.05); the expression of TGF-α in the liver tissues was significantly increased at the 4th week (P < 0.05); the expression of TGF-β1 in the liver tissues was gradually significantly increased in every model group (P < 0.05).
CONCLUSIONIn the formation process of cirrhosis, the expression of TGF-α was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-β1 was continuously increased. The characteristic dynamic changes of TGF-α and TGF-β1 might be related to sustained endotoxemia, the high level of TNF-α and hyperhomocysteinemia.
Alanine Transaminase ; blood ; Animals ; Carbon Tetrachloride ; Endotoxins ; blood ; Homocysteine ; blood ; Liver Cirrhosis ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor alpha ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; metabolism
6.Compatibility of geniposide and ginsenoside rgl: their regulating roles in secretion of anoxia induction injured microglia inflammatory cytokines.
Jun WANG ; Jin-Cai HOU ; Li-Hua XIANG ; Jie ZHANG ; Da-Hong JU
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(1):91-95
OBJECTIVETo clarify the protective roles of compatibility of geniposide and ginsenoside (Rg1) in regulating ischemia injured microglia homeostasis by comparing the difference in regulatory roles of geniposide, Rg1, or ginsenoside + Rg1 in balancing secretion of oxygen glucose deprivation induced microglia inflammatory cytokines.
METHODSThe mimic ischemia injured microglia model was induced by oxygen-glucose deprivation (OGD). Then geniposide, Rg1, or ginsenoside + Rg1 (Tongluo Jiunao Injection, TJI) was respectively added. The NO content was determined by Griess Reagent. The cyto activity was detected using cell count kit. Contents of TNF-alpha and TGF-beta and their expression levels were detected by ELISA and Western blot.
RESULTSGeniposide + Rg1 could significantly inhibit the release of NO, elevate the TGF-beta level, and decrease the content of TNF-alpha without influencing the cell survival. The two active ingredients played different therapeutic roles. The compatible use was obviously superior to use any one of the two active ingredients alone.
CONCLUSIONSGeniposide, Rg1, or Ginsenoside + Rg1 had regulating roles in balancing ischemia injured microglia homeostasis. Its mechanisms might be related to up-regulating the TGF-beta expression and down-regulating TNF-alpha expression.
Animals ; Ginsenosides ; pharmacology ; Hypoxia ; metabolism ; Iridoids ; pharmacology ; Mice ; Microglia ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
9.Hypoxia-inducible factor-1α expression in renal tissue of rats with paraquat poisoning.
Ying XIONG ; Rui-lan WANG ; Hui XIE ; Xue TANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2013;31(1):10-13
OBJECTIVETo observe the pathological changes of renal tissue in the rats with paraquat (PQ) poisoning as well as the serum creatinine (SCr) levels and expression levels of hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β (TGF-bgr;) in renal tissue at different time points after PQ poisoning, and to investigate the association of HIF-1α with renal injury after PQ poisoning.
METHODSForty-eight healthy male Sprague-Dawley rats were randomly divided into control group (n = 6) and PQ group (n = 42). The control group was given a single dose of 1 ml saline by gavage; the PQ group was given a single dose of 1 ml PQ (50 mg/kg), which was prepared by diluting 20% raw liquid of PQ with saline, by gavage. The PQ group was further divided into 2, 6, 12, 24, 48, 72 and 120 h PQ subgroups (n = 6 for each subgroup) to be examined at 2, 6, 12, 24, 48, 72, or 120 h after gavage. Their arterial blood was collected for blood gas analysis as well as blood lactic acid (BLA) and SCr measurement; renal sections were subjected to HE staining; the protein expression of HIF-1α and TGF-β in renal tissue was measured by Western blot.
RESULTSThe BLA level and SCr level began to rise at 6h after poisoning. Compared with the control group, the 6, 12, 24, 48, 72 and 120 h PQ subgroups had significantly increased BLA and SCr levels (P < 0.05); the 72 and 120 h PQ subgroup showed hypoxemia (P < 0.05). The protein expression of HIF-1α in PQ group increased significantly at 6h and reached the peak level at 72 h, with a significant difference from that in the control group at 6, 12, 24, 48, 72, and 120 h (P < 0.05). The protein expression of TGF-β in PQ group began to rise at 24 h, reached the peak level at 72 h, and declined at 120 h, with a significant difference from that in the control group at 24, 48, and 72 h (P < 0.05). The protein expression of HIF-1α was positively correlated with SCr level (r = 0.9308, P = 0.0008), uncorrelated with arterial partial pressure of oxygen (r = -0.6996, P = 0.0534), and positively correlated with BLA level (r = 0.9483, P = 0.0003). The pathological changes of renal tissue mainly included the degeneration and necrosis of renal tubular epithelial cells, which worsened as the time went on and appeared less severe at 120 h.
CONCLUSIONThe HIF-1α expression in renal tissue increases significantly in the early stage of PQ poisoning, which is associated with increased BLA and SCr levels and causes upregulated expression of TGF-β that promotes renal fibrosis.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Kidney ; metabolism ; pathology ; Male ; Paraquat ; toxicity ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; metabolism
10.Therapeutic efficacy of Jinshuibao capsules in treatment of silicosis.
Rong-ming MIAO ; Zhong-hua FANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(10):781-782
OBJECTIVETo investigate the therapeutic efficacy of Jinshuibao capsules in the treatment of silicosis.
METHODSA total of 270 patients with silicosis were randomly divided into treatment group (n = 141) and control group (n = 129). Both groups received conventional therapy. Additionally, the patients in the treatment group took 3 Jinshuibao capsules three times day for 2-3 courses of treatment (each course = 6 weeks). The therapeutic efficacy and the changes in tumor necrosis factor-α (TNF-α) and transforming growth factor-β(1) (TGF-β(1)) levels were observed after treatment.
RESULTSAfter treatment, cough, expectoration, chest pain, shortness of breath, and other respiratory symptoms were relieved significantly (P < 0.05). The treatment group showed significantly lower TNF-α and TGF-β(1) levels than before treatment and the control group (P < 0.05) and significantly higher forced vital capacity, forced expiratory volume in one second, and maximum mid-expiratory flow than before treatment and the control group (P < 0.05).
CONCLUSIONJinshuibao capsules can decrease inflammatory response, increase vital capacity and maximum voluntary ventilation, reduce airflow limitation, and improve quality of life and thus have good therapeutic efficacy in the treatment of silicosis.
Aged ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Middle Aged ; Phytotherapy ; Silicosis ; drug therapy ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; metabolism
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