RESUMEN
OBJECTIVE: This study aims to investigate the clinical value of serum Klotho and FGF23 in cardiac valve calcification in patients with chronic kidney disease (CKD). METHODS: In the present study, 180 patients with CKD, who were admitted to the department of nephrology of our hospital on April 1, 2016 (solstice, 2019), were selected as the main subjects. According to the CKD stage, these patients were divided into three groups: CKD2~3 group, CKD4 group, and CKD5 group. In each group, ultrasound was used to evaluate the cardiac valve calcification, and the independent risk factors for cardiac valve calcification were analyzed by Logistic regression. RESULTS: The levels of hemoglobin and blood calcium in CKD2~3 patients were higher than those in CKD4 and CKD5 patients, and the levels of hemoglobin and blood calcium in CKD5 patients were higher than those in CKD4 patients (P<0.05). Albumin was lower in CKD2~3 patients when compared to CKD5 patients while albumin was higher in CKD5 patients when compared to CKD4 patients (P<0.05). The serum levels of FGF23 was lower in CKD2~3 patients when compared to CKD4 and CKD5 patients while the serum levels of FGF23 was lower in CKD4 patients when compared to CKD5 patients (P<0.05). The serum levels of Klotho was higher in CKD2~3 patients, when compared to CKD4 and CKD5 patients, while the serum levels of Klotho was higher in CKD4 patients, when compared to CKD5 patients (P<0.05). The logistic regression analysis revealed that GFR, serum creatinine, FGF23 and Klotho were independent risk factors for cardiac valve calcification in patients with CKD. CONCLUSION: With the decrease of GFR in CKD patients, the serum levels of FGF23 increases, while the serum levels of Klotho decreases. Furthermore, the serum levels of FGF23 and Klotho are affected by various factors, and the levels of FGF23 and Klotho in CKD patients are negatively correlated. GFR, serum creatinine, FGF23 and Klotho are independent risk factors for heart valve calcification in patients with CKD.
RESUMEN
Vascular calcification (VC) plays as a critical role on cardiovascular disease (CVD) and acts as a notable risk factor in cardiovascular system. Vascular smooth muscle cells (VSMCs) calcification can be triggered by high phosphate treatment; however, the explicit mechanism remains unclear. In the present study, we isolated VSMCs from primary rat artery, applied ß-GP (ß-glycerophosphate) for inducing VSMCs calcification in vitro to explore the mechanism of phosphate-induced calcification in VSMCs. Alizarin red staining was performed to assess the mineralization in VSMCs. Calcium deposition experiment was taken to evaluate the calcium content. ALP staining was determined to assess the ALP activity. The recombinant adenoviruses were constructed for the overexpression of Klotho and FGF23, respectively. qRT-PCR and western blot analysis were subjected to measure the expression of Klotho/FGF23 and correlated genes among Wnt7b/ß-catenin pathway. We found that the calcium content was obviously increased and Alizarin red staining was positive in calcification group exposure with high phosphate in a time-dependent manner. The expression of Klotho and FGF23 was significantly decreased in the calcification group. However, overexpression of Klotho and FGF23 markedly reversed VSMCs calcification stimulating with high phosphate treatment. Moreover, Wnt7b/ß-catenin inhibitor DKK1 could partly attenuate the effect of high phosphate on calcified VSMCs. These findings demonstrated that Klotho/FGF23 axis could modulate high phosphate-induced VSMCs calcification via Wnt7b/ß-catenin signaling pathway. Our findings unravel that Klotho/FGF23- Wnt7b/ß-catenin axis functions as a crucial role in the VSMCs calcification.
Asunto(s)
Factores de Crecimiento de Fibroblastos/genética , Glucuronidasa/genética , Glicerofosfatos/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Calcificación Vascular/genética , Proteínas Wnt/genética , beta Catenina/genética , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Aorta/citología , Aorta/metabolismo , Calcio/metabolismo , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica , Glucuronidasa/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/farmacología , Proteínas Klotho , Masculino , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/farmacología , Transducción de Señal , Proteínas Wnt/antagonistas & inhibidores , Proteínas Wnt/metabolismo , beta Catenina/antagonistas & inhibidores , beta Catenina/metabolismoRESUMEN
The promoter of NAR gene in Magnaporthe grisea was isolated and sequenced. The promoter sequences contained the "TATA" box, the "CAAT" box, and binding sites for fungal regulatory proteins. Programs that predict promoter sequences indicated that promoter sequence lies between locations 430 and 857 of the NAR promoter fragment. GFP expression under the NAR promoter and NAR transcript analysis revealed that this promoter is activated primarily at the mycelial stage in the rice blast fungus and could be used to express native or extrinsic genes in the mycelia of the rice blast fungus.