Axon guidance molecules, slit glycoprotein (Slit) and Roundabout receptors (Robo) were firstly identified in the central neural system of Drosophila melanogaster. The Slit-Robo signal plays a crucial role in axon guidance, inflammation, tumor metastasis and angiogenesis, of which the role of Slit2-Robo pathway in angiogenesis has drawn a greater attention and still remains conflicting. Herein, we provide a review on the role of Slit2-Robo pathway in ocular angiogenesis and vascularization of other organs and systems. We hope this review will be the basis of further study on the mechanism of Slit2-Robo signaling on angiogenesis and provide new target for the therapy on ocular vascular disease
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
Objective To investigate the molecular signal mechanism of transform growth factor (TGF)-β induced arterial endothelial-mesenchymal transition. Methods Rat arterial endothelial cells were primarily cultured by ex-transplant method. The endothelial cells were incubated by combinant TGF-β (10 ng/mL) for 48 hours and then were detected by immunofluorescence staining and western blotting to observe the cell surface marker expression profile and Akt/mTOR signal activation. On the other hand, the endothelial cells were preincubated by Ly294002 (20 μmol/L) and rapamycin (10 nmol/L) to inhibit the Akt/mTOR signal, and then the cells were further treated with TGF-β (10 ng/mL) for 48 hours to observe the cell surface marker expression profile without Akt/mTOR signal activation. Results Rat artery endothelial cells by TGF-β after incubation, the expressions of smooth muscle cell markers α-smooth muscle actin (α-SMA) and smooth muscle-22α (SM-22α) were up-regulated, and the endothelial cell markers CD31 and vW factor were significantly down-regulated, at the same time, the expressions of phosphorylated Akt and mTOR were also up-regulated. However, after preincubation of Ly294002 (20 μmol/L) and rapamycin (10 nmol/L) to inhibit the phosphorylation of Akt and mTOR signal, above TGF-β-induced expressions of α-SMA and SM-22α in arterial endothelial cells were significantly suppressed and the expressions of CD31 and vWF were preserved. Conclusion TGF-β-induced arterial endothelial-mesenchymal transition is dependent on activation of Akt/mTOR signal, suggesting that Akt/mTOR-dependent arterial endothelial-mesenchymal transition would be one of the mechanisms for intima hyperplasia in transplant arteriosclerosis.
A new independent subtype CD4+ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.
Objective To explore the difference between the hemorheology levels and the expression of hypoxia inducible factor 1α/2α (HIF-1α/2α) in the peripheral blood mononuclear cells of the Tibetan and Han patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods This research recruited 30 high-risk Tibetan and Han patients with OSAHS, and 30 Tibetan and Han healthy volunteers at the same period. The whole blood viscometer was used to detect the high shear rate of whole blood viscosity, low shear rate of whole blood viscosity, plasma viscosity ratio, red blood cell aggregation index, and hematocrit in each group. RT-qPCR and Western blot assays were used to detect the mRNA and protein levels of phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), nuclear factor-κB (NF-κB) p65, HIF-1α and HIF-2α in peripheral blood mononuclear cells. Results The hemorheology level of Tibetan OSAHS patients was significantly higher than that of healthy Tibetans and Han OSAHS patients (P<0.05), and the hemorheology level of Han OSAHS patients was significantly higher than that of Han healthy people (P<0.05) . The mRNA and protein levels of PI3K, AKT, NF-κB p65 and HIF-1α in the peripheral blood mononuclear cells of Tibetan OSAHS patients were significantly higher than those of the healthy Tibetans or Han people, and these indexes of the Han OSAHS patients were significantly higher than those of the Han healthy people (all P<0.05), while HIF-2α mRNA and protein levels were significantly lower than those of healthy Han people (all P<0.05). Conclusion The upregulation of HIF-1α level and downregulation of HIF-2α expression in peripheral blood mononuclear cells of OSAHS patients depend on the activation of the PI3K/AKT/NF-κB p65 signaling pathway, and the hemorheological level of Tibetan OSAHS patients is higher than that of Han OSAHS patients.
Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane, and protects the cell against bactericidal agents. LPS, also called endotoxin synonymously, is well known as a potent inducer of the innate immune system that often causes septic shock in the intensive cares. Chemically, the amphiphilic LPS is made up of three parts, i.e. hydrophobic lipid A, hydrophilic core oligosaccharide chain, and hydrophilic O-antigenic polysaccharide side chain. Specially, the lipid A is known to be responsible for a variety of biological effects during Gram-negative sepsis. LPS can elicit a strong response from innate immune system and result in local or systemic adverse reactions. LPS can trigger massive inflammatory responses and may result in immunopathology, for which the molecular basis is mediated by the signal pathway of LPS. In recent years, a tremendous progress has been made in determining the associated proteins and receptors in the LPS signaling that leads to the disease. This review gives a summary of recent progresses of research on LPS and LPS receptors.
ObjectiveTo investigate the effect of PI3K/Akt/mTOR signaling pathway on liver injury induced by severe acute pancreatitis (SAP). MethodsForty healthy adult male Sprague-Dawley (SD) rats were randomly divided into 4 groups: Sham operation group (SO group), SAP group, PI3K inhibitor LY294002 group (LY294002 group), and mTOR kinase inhibitor rapamycin group (rapamycin group). The rat model with SAP was made by injection with 5% sodium deoxycholate through retrogradely bilio pancreatic duct. Serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate transaminase (AST) were detected through the inferior vena at 6 h after modeling. Pathologic change of the liver was observed under the light microscope. TUNEL analysis was used to detect apoptotic index (AI) of the heptocyte. Expressions of Akt, phosphated-Akt (p-Akt), mTOR, phosphated-mTOR (p-mTOR) protein were evaluated by Western blot. Results①Compared with the SO group, the serum levels of AMY, ALT, AST, and the hepatocyte AI were significantly increased among the other three groups (P < 0.05). Compared with the SAP group, the serum levels of AMY, ALT, AST, and the hepatocyte AI were significantly decreased in the LY294002 group and rapamycin group (P < 0.05).②Compared with the SO group, the damages of the liver tissues were aggravated among the other three groups. The pathologies of the liver tissues were ameliorated in the LY294002 group and rapamycin group as compared with the SAP group.③Compared with the SO group, the levels of p-Akt/Akt, p-mTOR/mTOR were significantly increased among the other three groups (P < 0.05). Compared with the SAP group, the levels of p-Akt/Akt, p-mTOR/mTOR were significantly decreased in the LY294002 group (P < 0.05), but in the rapamycin group, only the p-mTOR/mTOR level was significantly decreased (P < 0.05). ConclusionThe activation of PI3K/Akt/mTOR signaling pathway might be one of the reasons for the liver injury induced by SAP and blocking this signaling pathway might be a potential target of preventing progress of SAP and alleviating liver injury induced by SAP.
ObjectiveTo summarize the research progress of yes association protein (YAP) mechanisms regulatedby different signaling pathways in tumor cells in recent years. MethodsLiteratures about the recent studies on the YAP mechanisms regulated by different signaling pathways in tumor cells were reviewed according to the results searched from PubMed database. ResultsIn addition to the traditional HIPPO pathway for the regulation of YAP, YAP is also regulated by the Rho-GTPases, JNK, and Wnt/β-Catenin signal pathways. ConclusionYAP is regulated by many factors in tumor cells, so better understand the mechanisms of YAP regulated by different signaling pathways will provide anovel putative target fortumor diagnosis and therapy in the future.
Endometriosis (EM) is a common benign gynecological disease with complex pathogenesis and lack of unified understanding. In recent years, the theory of stem/progenitor cells has gradually been recognized by scholars. The presence of stem/progenitor cells in the endometrium and researchers’ understanding of stem/progenitor cell specific markers has been further developed, which is of great significance for sorting stem/progenitor cells and further elucidating their roles in the pathogenesis of EM. At present, more endometrial stem cell signaling pathways have been studied including Wnt, Hedgehog, Notch, phosphatidylinositol-3-kinase/protein kinase B, Smad/connective tissue growth factor, CXCL12/CXCR4, etc. These signaling pathways can regulate stem cell involvement in the pathogenesis of EM. Exploring how signaling pathways to regulate stem cell involvement in the pathogenesis of EM can help elucidate the specific pathogenesis of EM and provide new directions for its treatment. This paper will summarize them.