RESUMEN
AIMS: To investigate the role of Slit2 and Robo1 during the vascular disease of Polymyositis (PM) / dermatomyositis (DM). BACKGROUND: PM and DM are nonsuppurative inflammatory myopathies that mainly invade the skeletal muscles. OBJECTIVE: This study attempted to explore the specific mechanism of Slit2/Robo1 signaling pathway proteins during the vascular disease of PM/DM. METHODS: The mRNA expressions of Slit2 and Robo1 in the muscle tissue were detected by RT-qPCR between newly-diagnosed PM/DM patients and healthy controls. The number of Slit2 and Robo1 positive cells in the serial sections of muscle paraffin tissues was measured by immunohistochemistry in 10 patients with PM, 10 patients with DM and 20 healthy controls. RESULTS: The study results revealed that the mRNA expressions of Slit2 and Robo1 in muscle tissue in the PM and DM groups were higher than that in the control group (P<0.05). The positive expression rates of Slit2 and Robo1 in muscle tissue in the PM and DM groups were 80.0%, 80.0%, 70.0% and 70.0%, respectively. The difference was statistically significant (P<0.001), when compared to the control group (the positive expression rates were 0% and 10%, respectively). CONCLUSION: The activation of the Slit2/Robo1 signaling pathway is an important mechanism leading to the development of PM/DM.
Asunto(s)
Dermatomiositis/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Polimiositis/patología , Receptores Inmunológicos/metabolismo , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , China/epidemiología , Dermatomiositis/epidemiología , Dermatomiositis/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimiositis/epidemiología , Polimiositis/metabolismo , Transducción de Señal , Adulto Joven , Proteínas RoundaboutRESUMEN
This study aims to explore the roles of cysteine-rich protein 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and vascular endothelial growth factor (VEGF) in the vascular process of polymyositis (PM)/dermatomyositis (DM).Real-time quantitative polymerase chain reaction was used to determine the mRNA expression of Cyr61, CTGF, and VEGF in muscle tissues of initially treated PM/DM patients and controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of Cyr61, CTGF, and VEGF of initially treated PM/DM patients before and after treatment. Data were statistically analyzed using statistical software SPSS 17.0.The mRNA expression levels of Cyr61, CTGF, and VEGF in muscle tissues were higher in the PM and DM groups than in the control group (Pâ<â.05). Differences in the mRNA expression levels of Cyr61, CTGF, and VEGF in muscle tissues between the PM and DM groups were not statistically significant (Pâ>â.05). Before treatment, the serum levels of Cyr61, CTGF, and VEGF were higher in the PM and DM groups than in the control group (Pâ<â.05). Furthermore, in the PM and DM groups, the expression levels of Cyr61, CTGF, and VEGF in serum at 6 months after treatment were lower than those before treatment (Pâ<â.05).Cyr61, CTGF, and VEGF are involved in the pathogenesis of PM/DM. These may be involved in the pathogenesis mainly by affecting the formation of blood vessels and promoting inflammatory response. This suggests that microvascular lesions play an important role in the immune pathogenesis of inflammatory myopathy PM/DM.
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Factor de Crecimiento del Tejido Conjuntivo/genética , Proteína 61 Rica en Cisteína/genética , Dermatomiositis/genética , Polimiositis/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Factor de Crecimiento del Tejido Conjuntivo/sangre , Proteína 61 Rica en Cisteína/sangre , Dermatomiositis/sangre , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimiositis/tratamiento farmacológico , Polimiositis/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
OBJECTIVE: To observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS). METHODS: Of 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05). CONCLUSIONS: The results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.
Asunto(s)
Mal de Altura/metabolismo , Apoptosis , Células de la Médula Ósea/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Adulto , Mal de Altura/patología , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: The clinical manifestation of chronic mountain sickness (CMS) is polycythemia, pulmonary hypertension and mionectic blood. However, the pathogenesis of it is not identified now. So it is necessary to investigate the effects of the angiogenic growth factors on the pathophysiologic development of CMS. METHODS: The serum levels of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in 13 healthy Tibetan natives (Native), 17 healthy people in Xining (control group) and 35 CMS patients were determined by quantitative sandwich enzyme immunoassay. Meanwhile, the levels of Hb, Hct and SaO2 were determined. RESULTS: The serum levels of bFGF (107.26 +/- 7.86) ng/L, PDGF (630.18 +/- 9.89) ng/L and VEGF (543.74 +/- 6.76) ng/L in CMS were significantly higher than those in Natives (37.01 +/- 9.16; 292.16 +/- 6.88; 125.51 +/- 7.26) ng/L, and in control group (40.58 +/- 5.34; 287.68 +/- 8.33; 76.26 +/- 4.60) ng/L, respectively (P < 0.01). There was no difference between the natives and the control group in bFGF and PDGF (P > 0.05), while there was predominant difference between the Natives and the control group in VEGF (P < 0.01). There was a predominant positive correlation between the serum levels of bFGF, PDGF or VEGF and hemoglobin concentrations in CMS respectively (P < 0.01). And there were positive relations between angiogenic growth factors each other. CONCLUSION: The serum levels of bFGF, PDGF and VEGF in patients with CMS significantly increase, these angiogenic growth factors may play important role on the pathophysiologic development of CMS; the VEGF level likely contributes to the adaptation to plateau hypoxia in healthy Tibetan natives; the elevated bFGF, PDGF and VEGF levels are likely associated with excessive erythropoiesis in CMS.