Analysis of intercellular communication patterns in facioscapulohumeral muscular dystrophy based on single-cell nuclear transcriptome sequencing / 国际生物医学工程杂志

Objective:To analyze the patterns of intercellular communication in facioscapulohumeral muscular dystrophy (FSHD) by single-cell nuclear transcriptome sequencing.Methods:Bilateral asymmetrical lesions mouth orbicular muscle of two patients with FSHD and mouth orbicular muscle of two healthy patients were selected. Six samples were obtained, and were divided into control group, mild group and severe group. The normal orbicularis muscle sample was collected from 2 healthy individuals (the control group). The muscle samples in the mild group were from two patients with relatively normal muscle sides, and the samples in the severe group were from two patients with more severe muscle damage sides. Single-cell nuclear transcriptome sequencing was performed on all cells of the three groups. Reduced dimension clustering and cell definition were performed to identify differentially expressed genes and enrichment pathways. Intercellular communication patterns among major cell types and key signaling pathways were explored by cellular communication analysis.Results:Differential gene expression analysis of FSHD bilateral muscle samples identified 46 functionally differentially expressed genes associated with the disease in different cell types, related to apoptosis, oxidative stress, immune inflammation, and muscle function. Intercellular communication was generally increased in the severe group. Fibro-adipogenic progenitors (FAPs) and macrophages are important signaling sources in the abnormal muscle microenvironment of FSHD and are closely associated with disease progression. There are six unique signaling pathways in the mild group, including bone morphogenetic proteins (BMP), transforming growth factor-β (TGF-β), CXC motif chemokine ligand (CXCL), adhesion G protein-coupled receptor E5 (ADGRE5), interleukin-16 (IL-16), and wingless-type MMTV integration site family (WNT) signaling pathways. These signaling pathways are mainly involved in the interaction between macrophages, FAPs, and adipocytes and may be involved in the regulation of fat deposition and fibrosis changes in the diseased muscle.Conclusions:Single-cell nuclear transcriptome sequencing provides a relatively comprehensive pattern of intercellular communication between key cell types in FSHD, providing an appropriate reference for understanding the intercellular regulatory mechanisms of the FSHD muscle microenvironment.

Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

Design and applications of synthetic electroactive microbial consortia / 生物工程学报

Synthetic electroactive microbial consortia, which include exoelectrogenic and electrotrophic communities, catalyze the exchange of chemical and electrical energy in cascade metabolic reactions among different microbial strains. In comparison to a single strain, a community-based organisation that assigns tasks to multiple strains enables a broader feedstock spectrum, faster bi-directional electron transfer, and greater robustness. Therefore, the electroactive microbial consortia held great promise for a variety of applications such as bioelectricity and biohydrogen production, wastewater treatment, bioremediation, carbon and nitrogen fixation, and synthesis of biofuels, inorganic nanomaterials, and polymers. This review firstly summarized the mechanisms of biotic-abiotic interfacial electron transfer as well as biotic-biotic interspecific electron transfer in synthetic electroactive microbial consortia. This was followed by introducing the network of substance and energy metabolism in a synthetic electroactive microbial consortia designed by using the "division-of-labor" principle. Then, the strategies for engineering synthetic electroactive microbial consortiums were explored, which included intercellular communications optimization and ecological niche optimization. We further discussed the specific applications of synthetic electroactive microbial consortia. For instance, the synthetic exoelectrogenic communities were applied to biomass generation power technology, biophotovoltaics for the generation of renewable energy and the fixation of CO2. Moreover, the synthetic electrotrophic communities were applied to light-driven N2 fixation. Finally, this review prospected future research of the synthetic electroactive microbial consortia.

Research advances on extracellular vesicles-based regulation by traditional Chinese medicines and the relationship with TCM "Qi" / 药学学报

Extracellular vesicles (EVs) are an important type of active microvesicles. EVs encapsulate and transfer functional substances such as miRNAs, transcription factors and proteins, which are important vectors for cell communication and organ dialogue. In recent years, studies have shown that quite a number of Chinese medicinal herbs have the pharmacological effect of regulating EVs, and play a unique trans-organ and remote role in the treatment of diseases. Some Chinese medicinal herbs also contain plant-derived EVs themselves, which can be directly involved in the treatment of diseases. As one of the core theories of raditional Chinese medicines (TCM), Qi plays a variety of important roles in the physiological and pathological processes of human body and pharmacology. However, the scientific connotation of Qi′s role and the potential material carrier are still unclear. The latest research suggests that the effect of EVs is potentially related to that of Qi. Therefore, this paper reviews the effect of Qi nourishing Chinese medicinal herbs in regulating EVs in the treatment of cardiovascular diseases, nervous system diseases, liver diseases, renal diseases, malignant tumors and other diseases in recent years. EVs may play an important role in the pharmacological effect of some Chinese medicinal herbs in the treatment of diseases as an intermediary substance. EVs have the characteristics of long-distance transportation, which is consistent with the movement of Qi in TCM. EVs carry a variety of functional molecules, which is consistent with the function of Qi. As the potential material basis of Qi in TCM, the function of EVs is worth further study.

Research progress on the exosomes in ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Exosomes are extracellular vesicles of sizes ranging from 50-150nm in diameter. Exosomes can deliver bioactive molecules(<i>e.g.</i> proteins, lipids, DNA, microRNA, <i>etc.</i>)into target cells which play an important role in cell-cell communication. Researches demonstrated that exosomes mediated cell-cell communication can impact cell apoptosis, invasion, migration, immune response and oxidative repair ability of recipient cells. Recently, researches on exosomes developed rapidly in the field of ophthalmology. This review summarized the latest research progress of exosomes in ophthalmic diseases.

Research progress on the mechanism of endothelial cells injury in diabetic nephropathy / 解放军医学杂志

Diabetic nephropathy (DN) is one of the diabetic microvascular complications characterized by progressive protein uria and renal failure, which may eventually develop into end-stage renal disease (ESRD). Glomerular endothelial cells are one of the important components of glomerular filtration barrier. The structural and functional integrity of these cells are closely related to the maintenance of glomerular filtration function. Dysfunction of glomerular endothelial cells can lead to proteinuria, glomerulosclerosis and interstitial fibrosis, further damaging renal function and accelerating the progression of DN. The mechanisms leading to endothelial dysfunction include glucose metabolism disorder, oxidative stress, abnormal angiogenesis, inflammation and endothelial transdifferentiation. In recent years, it has been proposed that mechanisms such as intercellular communication, epigenetics and exosomes may be involved in the injury of diabetic nephropathy. In present paper, the research progress of related mechanisms was reviewed on the damage of glomerular endothelial cells in DN.

Progress in research on connexin 43 in oral squamous cell carcinoma / 口腔疾病防治

@#Cell gap junctions are a universal form of cellular connection in animal tissue that mediate the exchange of information, energy and material between adjacent cells. Clinical studies have demonstrated that the abnormal expression of the connexin 43 （Cx43） gene is closely associated with carcinogenesis and tumor progression. The present study reviewed relevant studies concerning the association between abnormal expression of Cx43 and oral squamous cell carcinoma as well as communication abnormalities of cell gap junctions.

Research progress on exosomes in radiotherapy for malignant tumors / 中华放射肿瘤学杂志

Exosomes are cell-derived vesicles and have biological activity.The diameter of exosomes is between 30 and 120 nm.Exosomes participate in the invasion,metastasis and multi-drug resistance of malignant tumors.In the field of radiotherapy,it has been proven that radiation-induced changes in the secretion of exosomes from tumor cells can affect intercellular communication and enhance the radiotherapy resistance of tumor cells.In this article,the research progress on exosomes in the radiotherapy for malignant tumors was reviewed.

Connexin 40-formed GJIC increases the phototoxicity of photodynamic therapy through ROS- and calcium-mediated pathways / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect of connexin (Cx) 40-formed gap junctional intercellular communication (GJIC) on Photofrin- photodynamic therapy (PDT) phototoxicity in Cx40- transfected HeLa cells and its potential mechanisms. METHODS HeLa cell line stably transfected to express Cx40 was seeded at high and low cell density, respectively, to assess in vitro photosensitivity using CCK8 assay. Western blot assay was performed to detect the expression of Cx40. The intracellular ROS and Ca2 +concentrations were determined using flow cytometer. 4-HNE and ceramide were measured using ELISA assay. RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx40 is not expressed or Cx40 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways. CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that mainte?nance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.

Effect of magnesium ion on human osteoblast activity

Magnesium, a promising biodegradable metal, has been reported in several studies to increase bone formation. Although there is some information regarding the concentrations of magnesium ions that affect bone remodeling at a cellular level, little is known about the effect of magnesium ions on cell gap junctions. Therefore, this study aimed to systematically investigate the effects of different concentrations of magnesium on bone cells, and further evaluate its effect on gap junctions of osteoblasts. Cultures of normal human osteoblasts were treated with magnesium ions at concentrations of 1, 2 and 3 mM, for 24, 48 and 72 h. The effects of magnesium ions on viability and function of normal human osteoblasts and on gap junction intercellular communication (GJIC) in osteoblasts were investigated. Magnesium ions induced significant (P<0.05) increases in cell viability, alkaline phosphate activity and osteocalcin levels of human osteoblasts. These stimulatory actions were positively associated with the concentration of magnesium and the time of exposure. Furthermore, the GJIC of osteoblasts was significantly promoted by magnesium ions. In conclusion, this study demonstrated that magnesium ions induced the activity of osteoblasts by enhancing GJIC between cells, and influenced bone formation. These findings may contribute to a better understanding of the influence of magnesium on bone remodeling and to the advance of its application in clinical practice.

Protective effect of Icariin against TGF-β1-induced injury of rat Leydig cells / 中华男科学杂志

<p><b>Objective</b>To study the effect of Icariin on rat Leydig cells with TGF-β1-induced injury.</p><p><b>METHODS</b>We determined the optimal concentration of Icariin for protecting primarily cultured Leydig cells against TGF-β1-induced injury by methyl thiazolyl tetrazolium assay. We detected the effects of Icariin on the secretion of estradiol (E2) and activity of aromatase in the injured Leydig cells by radioimmunoassay and Tritium water release experiment and its effect on the gap junctional intercellular communication (GJIC) between the Leydig cells by fluorescence distribution after photobleaching.</p><p><b>RESULTS</b>Different concentrations of Icariin showed different degrees of protective effect on the TGF-β1-treated Leydig cells, the effect observed at 20 μg/ml and at its optimum at 160 μg/ml. After treatment of the injured Leydig cells with Icariin at 160 μg/ml, significant improvement was observed in the E2 secretion and aromatase activity (P<0.01) as well as in the GJIC between the Leydig cells (P<0.01).</p><p><b>CONCLUSIONS</b>Icariin can effectively protect rat Leydig cells against TGF-β1-induced injury, which is largely attributed to its effects of increasing E2 synthesis, enhancing aromatase activity, and improving GJIC between Leydig cells.</p>

Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

Exosomes: mediators of communication in eukaryotes

In addition to the established mechanisms of intercellular signaling, a new way of communication has gained much attention in the last decade: communication mediated by exosomes. Exosomes are nanovesicles (with a diameter of 40-120 nm) secreted into the extracellular space by the multivesicular endosome after its outer membrane fuses with the plasma membrane. Once released, exosomes modulate the response of the recipient cells that recognize them. This indicates that exosomes operate in a specific manner and participate in the regulation of the target cell. Remarkably, exosomes occur from unicellular organisms to mammals, suggesting an evolutionarily conserved mechanism of communication. In this review we describe the cascade of exosome formation, intracellular traffic, secretion, and internalization by recipient cells, and review their most relevant effects. We also highlight important steps that are still poorly understood.

Effects of different types of Helicobacter pylori on the gap junction intercellular communication in GES-1 cells / 中南大学学报(医学版)

Objective To determine the effect of different types of Helicobacter pylori(H, pylori) on the gap junction intercellular communication (GJIC) in GES-1 cells, and investigate the types of H. pylorirelated to the dysfunction of GJIC. Methods Different types of H. pylori clinical strains were isolated and cultured, including the East Asian CagA-positive H. pylori( East Asian CagA +H. pylorl), Western CagA-positive H. pylori( Western CagA +H. pylori), and the CagA-negative H. pylori (CagA-H. pylori). We co-cultured these H. pyloristrains with GES-1 cells for 24 and 48h, respectively. The control group was cultured without any H. pylorifor 24 and 48 h. Change of the GJIC function in GES-1 cells was detected by the scrape-loading dye transfer (SLDT) technique. The cell proliferation of each group was examined by the methyl thiazolyl tetrazolium bromide (MTT) assay. Results The control group showed better GJIC function in the GES-1 cells, and the fluorescent dye migrated 4 - 5 rows to the adjacent cells at 24 and 48 h. Compared with the control group, the GJIC function of GES-1 cells in the CagA - H. pylori group decreased and the fluorescent dye migrated 3 rows to the adjacent cells. Compared with the control group and the CagA- H. pylori group, the GJIC function of GES-1 cells in the Western CagA + H. pylori group decreased and the fluorescent dye migrated 1 - 2 rows to the adjacent cells. The East Asian CagA * H. pylori group showed no GJIC function or weak GJIC function, and most of the fluorescent dye was confined to the area of scratched single row cells and only a few migrated 1 -2 rows to the adjacent cells. Difference in the cell proliferation between the CagA - H. pylorigroup and the control group was not significant. The cell proliferation of the Western CagA + H. pylori group and the East Asian CagA + H. pylori group at bacterium-to-cell ratio of 100:1 and 200:1 was higher than that of the control group. The cell proliferation of the East Asian CagA +H. pylori group at bacterium-to-cell ratio of 400:1 was significantly lower than that of the control group at 48 h. Conclusion H. pylorican inhibit the GJIC function in GES-1 cells, which may be associated with CagA +H. pylori, especially with East Asian CagA +H. pylori. The effect of H. pylori on the proliferation of GES-I cells is related to virulence factor CagA.

Regulation of Gap Junctional Intercellular Communication in Human Keratinocyte Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Unlike the normal skin, cholesteatomas characterized by hyperproliferative keratinocytes exhibits up-regulation of connexins (Cxs) and gap junctional intercellular communication (GJIC). Currently, there are no appropriate clinical methods that can inhibit cholesteatoma progression nor are there available optimal in vitro models of cholesteatomas. The objectives of this study were to identify the regulating materials that control GJIC using human keratinocyte cells (HaCaT) and to get preliminary information about how to inhibit cholesteatoma progression with an aim to make in vitro models. MATERIALS AND METHOD: Acetic acid (AA), H2O2, dexamethasone, retinoic acid (RA), or green tea extracts-epicatechin (EC) and epigallocatechin gallate (EGCG) were used for this study. After HaCaT cells were cultured with chemicals for 24 hours, cytotoxicity was quantitatively analyzed by cell counting and Neutral-red uptake test. Reverse transcriptase-polymerase chain reaction, Western blot and immunocytochemistry were performed to analyze the change of Cx expression. GJIC was functionally evaluated with scrape-loading dye transfer (SLDT). RESULTS: After the 24-hour culture, H2O2 or EGCG (100 microM) were observed to have interfered with cell growth. In the Western blot, Cx26 and Cx30 showed higher up-regulation by EGCG or dexamethasone, but less down-regulation by AA or H2O2 than the control. In comparison with the control, immunocytochemistry (Cx26, Cx43) showed less expression and abnormal location of Cxs under AA, H2O2, or 50 microM EGCG than the control, and increased up-regulation or equal expression under 5microM EGCG, EC, RA, or dexamethasone was greater than the control. In SLDT, dye transfer was significantly lower in AA-, H2O2-, dexamethasone-, or RA-treated cells than in the control cells. EC showed higher dye transfer than the control cells. CONCLUSION: The expression of Cxs and GJIC on human HaCaT keratinocytes can be up- or down-regulated by chemicals such as AA, H2O2, dexamethasone, or EC. These results may be useful information in understanding the progression or inhibition mechanisms of cholesteatomas.

Research of UVA in affecting Cx43 protein among rabbit lens epithelia cells / 重庆医科大学学报

Objective:To probe the mechanism of inhibition in gap junction-mediated intercellular communication (GJIC) of rabbit lens epithelia cells(RLECs) irradiated by UVA. Methods:RLECs of 2～3 generation were divided into normal control group and ultraviolet irradiation group (The UV intensity was 0.2 mW/cm2 under a UV lamp with fixed position 50 cm, RLECs were exposed to ultraviolet lamp at different times: 5,10,15 minutes). Western blot techniques were employed to detect the protein levels of Cx43 irradiated by UVA. By indirect immunofluorescence histochemistry we analyzed the localization of Cx43 in the RLECs. Results:In UVA irradiation group and normal control group,there was expression of Cx43. With the increasing intensity,the expression of Cx43 was decreasing. The immunnostaining of Cx43 in RLECs revealed that the internalization of Cx43 from membrance to plasma and nuclear was found in UVA irradiated RLECs. Conclusion: Cell molecule level study proved UVA irradiation can reduce GJIC of RLECs,which wis associated with perturbations in localization and number of Cx43 among RLECs.

Study on Cx43 expression and function of GJIC in ectopic and eutopic endometrial stromal cells in vitro / 重庆医科大学学报

Objective:To investigate Cx43 expression and gap junctional intercellular communication(GJIC) in ectopic and eutopic endometrial stromal cells in endometriosis(EMs),and to explore the influence of aberrant GJIC in stromal cells on pathogenesis of EMs. Methods:The stromal cells were isolated from samples including 24 ectopic endometriotic tissues located in ovaries,41 eutopic endometria with endometriosis and 30 normal endometria. The endometrial stromal cells models were established in vitro by being cultured in manual conditions mimicked with estrogen and progesterone. Laser scanning confocal microscopy(LSCM) was used to determine the expression of Cx43 protein and the function of GJIC in three groups stromal cells. Results:The success rate of isolation and culture of endometriotic stromal cells was 45.8%(11/24);of eutopic endometrial stromal cells with EMs was 92.7(38/41);of normal endometrial stromal cells was 93.3%(28/30). The purities of ectopic and eutopic endometrial stromal cells were 95% and 98% respectively. The level of Cx43 protein and the function of GJIC in stromal cells from ectopic endometrial tissues were much lower than those from the other two groups,the highest level of Cx43 protein and the function of GJIC were observed in normal endometrial stromal cells group,and the differences among these groups were significant (P﹤0.01). Conclusions:(1) It will be helpful to establish models of normal,ectopic and eutopic endometrial stromal cells in vitro simultaneously when investigating the pathgenesis of EMs. (2)Downregulation of Cx43 expression and aberrant function of GJIC are related to pathogenesis of EMs. Regulation of Cx43 or GJIC in endometrial stromal cells is implied to be a potential strategy to treat EMs.

Effect of PM2.5 on Gap Junctional Intercellular Communication in Neonatal Rat Cardiomyocytes / 环境与健康杂志

Objective To investigate the effects of PM2.5 on gap junctional intercellular communication (GJIC) between rat cardiomyocytes. Methods Primary cultured cardiomyocytes were prepared from 1-day-old Sprague-Dawley rats and exposed to PM2.5(1,10,100 ?g/ml)for 24 hours. The GJIC between cardiomyocytes was detected by the scrape loading dye transfer assay. The distribution and density of connexin43(Cx43) in the cells was detected by indirect immunofluorescence and the expression of Cx43 was detected by western blotting. Results The gap junctional intercellular communication between cardiomyocytes was significantly inhibited by PM2.5 in a dose-dependent manner. The fluorescence density of Cx43 was significantly decreased in PM2.5-treated cells,and the expression of Cx43 was also slightly decreased. Conclusion PM2.5 can inhibit GJIC between cardiomyocytes,which may be mediated by the decreased expression and aberrant distribution of Cx43 in PM2.5-treated cells.

Altered Expression of Connexin-43 and Impaired Capacity of Gap Junctional Intercellular Communication in Prostate Cancer Cells / 华中科技大学学报（医学）（英德文版）

Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elucidate the reason why the so-called "bystander effect" mediated by thymidine kinase (TK) suicide gene therapy on PCa cells is not of significance and to explore the role of GJIC in PCa carcinogenesis.mRNA and protein expression of Cx43 in a PCa cell line PC-3m was detected by reverse-transcription polymerase chain reaction (RT-PCR) and strapt-avidin-biotin-enzyme complex (SABC) immunohistochemical staining, and inherent GJIC of PC-3m cells was assayed by scrape-loading and dye transfer (SLDT) assay. The expression of Cx43 in human normal and malignant prostate tissues was determined by SABC immunohistochemistry as well. It was found that Cx43 mRNA and protein expression in PC-3m cells was slightly reduced as compared with positive controls and the location of Cx43 protein was aberrant in cytoplasm rather than on membrane. Assessment of paraffin sections demonstrated that the expression of Cx43 protein in PCa cells was abnormally located and markedly diminished as compared with normal prostatic epithelial ones, displaying a negative correlation to the pathological grade (χ2=4.025, P＜0.05). Additionally, capacity of inherent GJIC in PC-3m cells was disrupted, which was semi-quantified as (+) or (-). It was indicated that both down-regulated expression of Cx43 mRNA and aberrant location of Cx43 protein participated in the mechanisms leading to deficient GJIC in PC-3m cells. Lack of efficient GJIC is a molecular event, which may contribute not only to limited extent of "bystander effect", but also to initiation and progression of prostatic neoplasm.

Progress in The Reverse Signal Transduction Mediated by Eph-ephrin / 生物化学与生物物理进展

Bidirectional signal transduction is a newly elucidated mechanism in intercellular communication. The bidirectional signal transduction mediated by the Eph-ephrin is an important representative in this field. The Eph family receptor tyrosine kinases and their membrane-bound ligands, the ephrins, play pivotal roles in the development of nervous system, angiogenesis, etc. The signal transduction into cells by Eph receptors is the forward signal, whereas the signal transduction by ephrins is the reverse signal. Based on their molecular structures, the ephrins can be divided into two subclasses, i.e. ephrinA and ephrinB. The ephrinBs are transmembrane proteins, which can activate FAK, JNK and Wnt signal transduction pathways through phosphotyrosine-dependent signaling and PDZ-binding motif-dependent signaling. The ephrinAs are glycosylphosphotidylinositol (GPI) anchored proteins, which can also mediate reverse signal transduction.