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@#Glaucoma is the leading cause of irreversible vision loss in the world. Drugs and surgery can be used to control intraocular pressure, however, they can't reverse the apoptosis of retinal ganglion cells effectively. With the development of genetics and molecular biology, a large amount of research on the pathogenesis of glaucoma has been conducted. This review discusses the potential role of Rho/ROCK, TGF-β/Smad, PI3K/Akt, Nrf2/Keap1/ARE and BDNF/TrkB signaling pathways in the pathogenesis of glaucoma, and expects to provide new ideas and methods for the treatment of glaucoma.
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Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, NF-kB, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.
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Animals , Humans , Mice , Dataset , DNA , Gene Expression , Lung Injury , Lung , NF-kappa B , Signal Transduction , Stem Cells , Transcription Factors , TranscriptomeABSTRACT
The etiology of pulmonary fibrosis is complex. The occurance and development of this disease involve many cell signal transduction pathways, including MAPK signaling pathway, JAK-STAT signaling pathway, Smad signaling pathway, PI3K-Akt signaling pathway, NF-κB signaling pathway and so on. Numbers of experiments have shown that intervention in signal transduction pathways with TCM can delay the progression of fibrosis, which provides good therapeutic methods for this disease. This article reviewed study on TCM intervention in different signal transduction pathways in the pulmonary fibrosis in China.
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Objective:To explore the mechanism of promotion effect of juglone combined with cisplatin on the apoptosis of human cervical cancer HeLa cells,and to clarify the effects of its associated signal transduction pathways.Methods:The HeLa cells at logarithmic growth phase were divided into control group,juglone group, cisplatin group and juglone combined with cisplatin group (combined treatment group).The inhibitory rates of proliferation of HeLa cells were detected by MTT assay.The apoptosis was detected by Hoechst 33258 staining. The expressions of Bcl-2, Bax and caspase-3, AKt, and pAKt were detected by Western blotting method. Results:The MTT results showed that the HeLa cell proliferation at 24,48 72 h in each drug group was inhibited;compared with control group,the profileration of HeLa cells in juglone group and cisplatin group was significantly inhibited,especially in combined group. Compared with single drug group,the inhibitory effect in combined treatment group was more significantly.After treatment for 12 h,the typical morphological changes of apoptosis were found in juglone group and cisplatin group by Hoechst 33258 staining,especially in combined treatment group. The Western blotting results showed that the expression levels of Bcl-2 and pAKt in HeLa cells in juglone group and cisplatin group 12 h after treatment were decreased obviously,whereas the expression levels of Bax,Caspase-3,and AKt were increased significantly, especially in combined treatment group compared with control group. Conclusion:Juglone combined with cisplatin could inhibit the PI3K/AKt pathway,thereby promoting the apoptpsis of HeLa cells.
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The intracellular signal transduction pathways play an important role in the occurrence and development of thyroid cancer.Mitogen activated protein kinase (MAPK) signal transduction pathway,phosphatidylinositol 3-kinase (PI3K)-AKT pathway,NF-κB pathway and RASSF1-MST1-FOXO3 pathway affect the occurrence and development of thyroid cancer by modulating the activity and expression of specifical proteins,and determine the growth and apoptosis of thyroid cancer cells.
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Sox-2(SRY related HMG box-2)is an essential embryonic stem cell gene and a necessary transcription factor for maintaining the proliferation and self-renewal capability of embryonic stem cell .Sox-2 is involved in complex cell signal transduction pathway network and adjusting biological behavior of cells .Expression of Sox-2 is adjusted by different factors in transduction , transla-tion and post-translation levels .In recent years , increasing evidences indicate Sox-2 has an important role in tumor development , growth, proliferation, and metastasis, which is involved in various biological behavior of tumor cells in many types of tumors .This pa-per reviews the role of Sox-2 in adjusting tissue and tumor development and complex cell signal transduction pathway network of Sox -2 and clinical values of Sox-2 in tumor diagnosis and treatment until now .
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Objective To detect the expressions of BMPR Ⅰa of BMPs/BMPR/Smads signaling transduction pathway in human brain glioma ,to research the role of its in tumorigenesis and progression of brain glioma and its correlation to clinical pathology . Methods The mRNA and protein expressions of BMPR Ⅰa was detected in 20 normal brain tissues and 40 samples with human glioma by RT-PCR and SABC immunohistochemical methods ,repectively ,and analyzed the correlation with the patient′s age ,gender and pathological grade .Results Compared with normal brain tissues ,BMPR Ⅰa mRNA and protein expressions in human glioma were reduced significantly ,especially in Ⅲ and Ⅳ stage tumor tissues .The difference was not related with the patient′s age and gender .Conclusion In progression of glioma ,BMPR Ⅰa may play a role in restraining ,and has nothing to do with age and sex .
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Intercellular adhesion molecule -1 is closely related to the occurrence,development and me mastasis of liver cancer.A variety of inflammatory cytokines and stimulus effect on the expression of Intereclluar adhesion molecule-1 through Nuclear factor-kappa B signal transduction pathways.In the stage of inflammation,hepatocirrhusis and tumor,Intercelluar adhesion molecule-1 is expressed differently,and makes different effects on different cells,to promote the occurrence and metastasis of tumor.Diagnostic significance of Intercelluar adhesion molecule1 is to diagnose hepatocellular carcinoma with AFP-negative or suspected-positive more early.What's more it can prognosticate the metastasis and prognosis of liver cancer as a biomarker.Many new treatments of liver cancer are based on the effects on Intercelluar adhesion molecule-1 in different levels producing antitumor function.
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Brain-derived neurotrophic factor(BDNF)belongs to the neurotrophin family and abundantly expressed in the nervous system.It plays an essential role in the survival,development,function,morphogenesis and plasticity of neurons by binding to the tyresine receptor kinase B(TrkB)and subsequent downstream activation of several signal transduction pathways in the nervous system. The PI3K/Akt and the MAPK/ERK DathWays ale two major intracellular signaling network activated by BDNF involved in survival of neurons.Becently.it is investigated that BDNF and TrkB are involved in the pathophysiology of hypoxic ischemic brain damage (HIBD)and in the mechanism of action of therapeutic agents.Therefore we image changing the internal or external condIitions can increase the expression of BDNF,thsu reduce the nervous system damage of HIBD.
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Purpose To investigate the effect of interleukin-10(IL-10)on IL-15mRNA and IL-6mRNA in Hela cells induced by lipopolysaccharide(LPS)and to analyze their activiated signal transduction pathways.Methods Extracted total RNA and total proteins of cultured Hela cells,which were treated with different concentrations of LPS,or IL-10 alone or in combined use,were to analyze the levels of IL-15mRNA and IL-6mRNA using RT-PCR and to analyze the expression of signal transduction pathway proteins using Western blot.Results RT-PCR indicated that expression of IL-15mRNA and IL-6mRNA in Hela cells strikingly increased after 12 h using 1 ng-10μg LPS(P＜0.01 vs control),which had dose-dependence and achieved peak value using 100 ng/mL.During 0-24 h,expression of IL-15mRNA and IL-6mRNA strikingly increased with time changing(P＜0.01 vs control),which had time-dependence and achieved peak value at 12 h.Expression of IL-15mRNA and IL-6mRNA had no conspicuous difference in Hela cells treated with IL-10(10 ng/mL)alone(P＞0.05 vs control).Different concentrations of IL-10 1,10,100 ns/mL)markedly downregnlated expression of IL-15mRNA and IL-6mRNA in Hela cells induced by LPS.Furthermore,the effect of inhibition will be more obvious with dose increasing.Western blot indicated that LPS upregulated expression of IL-15mRNA and IL-6mRNA by phosphorylation of PI3K/AKT and ERK1/2.IL-10 blocked phosphorylation of AKT,but could not affect phosphorylation of ERK1/2.Conclusion IL-10 downregulated the expression of inflammatory cytokines IL-15 and 1L-6 induced by LPS,which may correlate with the fact that phosphorylation of AKT was blcoked by IL-10.Therefore,IL-10 may be used to prevent and treat some clincal infective diseases.
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Adipose tissue is traditionally regarded only as an energy storage and a filler between tissues/organs. However, other important functions of adipose tissue begin to be discovered with the discovery of adipokines. Adipose tissue is also an endocrine organ, which secrets different kinds of adipokines, affecting the target organs through autocrine, paracrine and the blood circulation, and playing important roles in the pathogenesis of the obesity, insulin resistance and type 2 diabetes mellitus. This paper reviews the signal transduction pathways of adiponectin, leptin and resistin, and their changes during obesity.
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It has been long thought that the brain reorganizes itself in response to environmental needs. Sensory experiences coded in action potentials are the mean by which information on the surroundings is introduced into neuronal networks. The information approaching the brain in the form of electrochemical codes must then be translated in biochemical, epigenetic and genetic ones. Only until recently we have begun understanding the underpinning of such informational transformations and how this process is expressed as neuronal plastic responses. Central for our comprehension of this matter is the finding that signals transduction cascades can modify gene expression by remodeling the chromatin through epigenetic mechanisms. Hence, chromatin remodeling seems to be the process by which experiences are imprinted.
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Epigenesis, Genetic , Gene Expression , Neuronal Plasticity , Signal TransductionABSTRACT
Apoptosis is a main death pattern in many nervous system disease.Erythropoietin(Epo)has been originally characterized as the principal regulator of erythropoiesis by stimulating the proliferation and differentiation of erythroid precursor cells.In recent years,many experimental studies have shown that both Epo and EpoR(erythropoietin receptor)are functionally expressed in the nervous system and that this cytokine exerts a remarkable neuroprotection against nerve cell apoptosis.This article reviews neuroprotective of Epo against apoptosis and outline the involved molecular mechanisms.
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Aim To study the effect of rhynchophylline and isorhynchophylline on the proliferation of rat vascular smooth muscle cell(VSMCs)induced by angiotensin Ⅱ(AngⅡ)and discuss it's mechanism.Methods A cell proliferating model of VSMC induced by AngⅡ was established.The proliferative activity of VSMC with rhynchophylline and isorhynchophylline was analyzed by MTT method.The effect of rhynchophylline and isorhynchophylline on cell cycle of VSMC was observed by flow cytometry.The effect of rhynchophylline and isorhynchophylline on protein of AT1R gene,NF-?B gene,Stat3 gene,c-Myc gene and c-Fos gene in VSMCs was observed by flow cytometry.The effect of rhynchophylline and isorhynchophylline on c-Myc mRNA and c-Fos mRNA in VSMCs was observed by RT-PCR.Results The proliferation of VSMC induced by AngⅡ stimulation was inhibited by rhynchophylline and isorhynchophylline,and the cell numbers of G0/G1 phase were increased and those of S phase were decreased markedly.At the same time,high expression of the protein of c-Myc gene,c-Fos gene,AT1R gene,NF-?B gene and stat3 gene stimulated by AngⅡ could be inhibited by rhynchophylline and isorhynchophylline significantly,and high expression of c-Myc gene mRNA and c-Fos gene mRNA stimulated by AngⅡ could also be inhibited by rhynchophylline and isorhynchophylline significantly.Conclusions The proliferation of VSMCs induced by AngⅡ can be inhibited by rhynchophylline and isorhynchophylline.The mechanisms are related to preventing VSMCs from G0/G1 phase entering S phase,and down regulating the expression of protein of AT1R gene,NF-?B gene,Stat3 gene,c-Myc gene and c-Fos gene.In addition,c-Myc gene mRNA and c-Fos gene mRNA expression are down regulated as well.
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Objective To study the regulating effect of in the regulation of cell surface receptor linked signal transduction pathway-related genes on rat liver regeneration(LR) at transcriptional level. Methods Genes involved in the above pathways were obtained by data collection and literature review.The gene expression changes during LR were checked by Rat Genome 230 2.0 array,and LR-related genes were identified by comparing gene expression difference between partial hepatectomy(PH) and sham operation(SO) groups. Results 491 genes were identified as LR-related.There were 742 kinds of interactive relations in 226 before-mentioned genes.In the 12 kinds of signaling pathways cytokine and chemokine mediated,enzyme linked receptor,G-protein coupled receptor,glutamate,antigen receptor-mediated,integrin-mediated,lipopolysaccharide-mediated, Notch,osmosensory,smoothened,Toll and Wnt——the numbers of up-regulated and down-regulated LR-related genes were 26 and 23,164 and 54,59 and 51,5 and 1,22 and 14,21 and 10,1 and 1,4 and 11,23 and 11, 32 and 17 respectively.In LR,the numbers of up-regulated and the down-regulated genes were 188 and 128,464 and 190,308 and 207,13 and 5,88 and 46,123 and 50,2 and 1,20 and 43,148 and 30,174 and 62 in the corresponding pathways.The genes which up regulated mainly occurred 0.5-16,30,42,54,96 hours and which down regulated mainly occurred 18-24,36,60-72,120-168 hours.Conclusion In liver regeneration,lipopolysaccharide-mediated and osmosensory signaling pathway have less effect,and the smoothened signaling pathway's role is attenuated,but the activities of the other 9 pathways are enhanced.