RESUMEN
Follicle-stimulating hormone (FSH) is a pituitary glycoprotein that regulates follicle maturation through its binding to follicle-stimulating hormone receptor (FSHR). Endothelial cells express FSHR, but its exact role in endothelial cells remains unclear. Here we show that FSHR expression was detectable in human umbilical vein endothelial cells (HUVECs). FSH stimulation promoted HUVECs migration but not proliferation. Because FSHR is a GPCR, FSH treatment triggers the activation of cAMP-PKA signaling pathways, and the JAK-STAT, PI3K-AKT, and JNK-MAPK pathways. RNAi of FSHR dramatically attenuated the activation effect of FSH on HUVECs migration, as well as the related signaling pathways. Treatment of FSH in HUVECs also transcriptionally upregulated the expression of VAV3 and LAMA2, suppression either of VAV3 or LAMA2 by RNAi attenuated the FSH's effect on HUVECs migration. All of these results indicated a functional role of FSH in the regulation of endothelial cells.
Asunto(s)
Movimiento Celular , Hormona Folículo Estimulante Humana/metabolismo , Hormona Folículo Estimulante , Receptores de HFE/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de HFE/genética , Transducción de SeñalRESUMEN
PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-α, IL-1ß, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-α, IL-1ß, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects.
Asunto(s)
Lesión Renal Aguda/patología , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Dexmedetomidina/farmacología , Riñón/irrigación sanguínea , Daño por Reperfusión/complicaciones , Actinas/análisis , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Animales , Nitrógeno de la Urea Sanguínea , Western Blotting , Creatinina/sangre , Proteína HMGB1/análisis , Inmunohistoquímica , Inflamación/etiología , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/análisis , Interleucina-1beta/análisis , Riñón/química , Masculino , ARN/análisis , ARN/aislamiento & purificación , Distribución Aleatoria , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Daño por Reperfusión/patología , Receptor Toll-Like 4/análisis , Factor de Necrosis Tumoral alfa/análisisRESUMEN
PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects.
