GLGZD improves cerebral ischemia-reperfusion injury in rats by inhibiting microglial activation / 中国药理学通报

Aim To study whether GLGZD exerts brain protection by affecting the activation of cortical microglia in cerebral ischemia-reperfusion rats. Methods The nylon thread plug was used to establish the MCAO model. After GLGZD treatment for seven days, mNSS was used to evaluate the neurological function of each group of rats, MRI to detect cerebral infarction volume in rats, TUNEL to detect the apoptotic rate of nerve cells, immunohistochemistry to detect TNF-α protein expression in ischemic cortical brain tissues, and RT-qPCR to detect mRNA expression of neuron-microglia interaction-related factors TWEAK, Fnl4, NIK, Rel B, CCL21, CXCR3 and microglial activation marker IBA-1 in ischemic cortical brain tissues. Results GL-GZD could significantly improve the neurological function of MCAO rats, and markedly reduce the infarct volume and apoptosis of ischemic cortical neurons in MCAO rats. It also could significantly down-regulate the expressions of TNF-a protein and TWEAK, Fnl4, NIK, Rel B, CCL21, CXCR3 and IBA-1 mRNA in ischemic cortex of MCAO rats. Conclusions GLGZD can significantly improve cerebral ischemia-reperfusion injury in rats, which may be related to inhibition of microglial cell activation by affecting TWEAK/Fn14/ CCL21/CXCR3 signaling pathway.

Effects of cryptotanshinone on airway inflammation models in asthmatic mice through tweak/fnl4 and tgf-pl/smads signaling pathways / 中国药理学通报

Aim To explore the therapeutic effect of cryptotanshinone(CTS) on airway remodeling model of asthmatic mice, and the relationship between its mechanism and the TWEAK/Fn14 and TGF-β1/Smads signaling pathway. Methods Forty female BALB/c mice were used for our study, eight mice as a group, and were assigned into five groups, namely, control group, OVA model group, CTS treatment group (20, 40 mg·kg-1), and Dex positive control group (1 mg·kg-1). HE and PAS staining were used to observe lung histopathological changes in mice; Diff-Quick staining was employed to count the types of cells; ELISA was used to detect the contents of proinflammatory cytokines in BALF; Western blot was applied to analyze the contents of TWEAK, Fn14, TGF-β1, Smad2/3, Smad4 in lung tissues; immunohistochemical method was used to detect the expression levels of TWEAK and TGF-β1 in lung tissues. Results CTS reduced the exudation of inflammatory cells and proliferation of goblet cells; CTS inhibited the generation of EOS, NEU, LYM and the total cells; CTS could reduce the level of proinflammatory cytokines of airway inflammation; the results of Western blot showed that CTS inhibited the protein expression of TWEAK, Fn14, TGF-β1, Smad2/3 and Smad4; immunohistochemical results indicated that CTS increased the expression of TWEAK and TGF-β1 in lung tissues. Conclusions CTS has therapeutic effect on the OVA-induced airway inflammation mouse model through TWEAK/Fn14 and TGF-β1/Smads signaling pathways.

Effects of fibroblast growth factor inducible 14 (Fn14) on high glucose induced-cardiomyocyte hypertrophy / 中华内分泌代谢杂志

Objective To investigate the effect and mechanisms of factor fibroblast growth factor inducible 14(Fn14)in the high glucose induced-cardiomyocyte hypertrophy. Method To observe the expression of collagenⅠ, connective tissue growth factor ( CTGF ) , transforming growth factor-β1 ( TGF-β1 ) , and Fn14 in high glucose induced-cardiomyocyte hypertrophy. Fn14 expressions was down-regulated by siRNA interference technique, and then the expressions of collagen Ⅰ, CTGF, and TGF-β1 were observed, and the mechanism was also explored. Results The expression of collagen I, CTGF and TGF-β1 was significantly up-regulated after high glucose induced-cardiomyocyte hypertrophy for 72 h. At the same time, the expression of Fn14 was increased after 72 h-treatment, and reached the peak at concentration of 30 mmol/L high glucose. High glucose could not up-regulated the expression of collagenⅠ, CTGF, and TGF-β1 after siFn14 interference, while the same result was observed in the expression of p-JNK. Conclusion The expressions of collagenⅠ, CTGF, TGF-β1, and Fn14 in cardiomyocyte of neonatal rats were induced by high glucose. While Fn14 expression was inhibited, the expressions of collagenⅠ, CTGF, and TGF-β1 were down-regulated, which seems to be involved with p-JNK signaling pathway.

The Effects of TWEAK, Fn14, and TGF-beta1 on Degeneration of Human Intervertebral Disc

OBJECTIVE: The purpose of this study is to explain the effect and reciprocal action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-beta1 (TGF-beta1) on degeneration of human intervertebral disc (IVD). METHODS: Human intervertebral disc tissues and cells were cultured with Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in 37degrees C, 5% CO2 incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an antagonistic receptor for TWEAK and TGF-beta1, the level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic acid (mRNA) levels were estimated by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: When human IVD tissue was cultured for nine days, the sGAG content was elevated in proportion to culture duration. The sGAG was decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9 mRNA levels decreased with TWEAK in IVD tissue TGF-beta1 20 ng/mL elevated the sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK was increased with Fn14 or TGF-beta1 but the result was insignificant statistically. TGF-beta1 increased the Sox9 mRNA expression to 180% compared to control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK were increased with TGF-beta1 in primary cultured IVD cells, however, Fn14 did not show increasing effect on Sox9 and versican. CONCLUSION: This study suggests that TWEAK would act a role in intervertebral disc degeneration through decreasing sGAG and the mRNA level of versican and Sox9.

TNEAK-Fn14 Pathway and Central Nervous System / 国际脑血管病杂志

Tumor necrosis factor-like weak inducer of apoptosis(TWEAK)is a new member of the tumor necrosis factor family.After TWEAK binding to its receptor Fn14.it induces extensive biological activities.TWEAK-Fn14 pathway participates in pathophysiological mechanisms of cell apoptosis,regulation of the blood-brain barrier permeability and inflammation in central nervous system,and it is closely correlated with the diseases such as ischernic stroke.multiple sclerosis and gliocytoma.