phenanthrenes and Renal-Insufficiency--Chronic

Vascular calcification is common in chronic kidney disease (CKD) patients, while erythropoietin (EPO) is widely used in the treatment of renal anemia in CKD patients, whether there is a link between the two is still not clear.. The primary rat vascular smooth muscle cells (VSMCs) and CKD rats were treated with EPO and the calcium deposition was observed by alizarin red staining, von Kossa staining and calcium quantification. Activation of JAK2/STAT3/BMP-2 axis and NF-κB signaling pathways was investigated by Western blotting.. EPO-induced calcium deposition in VSMCs and significantly potentiated calcification in CKD rats. Furthermore, EPO activated JAK2/STAT3/BMP-2 axis, NF-κB pathway and the pro-calcification effect of EPO was partially blocked by the STAT3 inhibitor (Cryptotanshinone) or NF-κB inhibitor (BAY 11-7082), respectively, in vitro.. EPO could promote VSMCs calcification in vitro and in vivo and this effect may be achieved through the JAK2/STAT3/BMP-2 axis and NF-κB pathway.

Topics: Alkaline Phosphatase; Anemia; Animals; Bone Morphogenetic Protein 2; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Erythropoietin; Gene Expression; Janus Kinase 2; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NF-kappa B; Nitriles; Phenanthrenes; Phosphorylation; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Signal Transduction; STAT3 Transcription Factor; Sulfones; Up-Regulation; Vascular Calcification

Chronic kidney disease (CKD) is a common cause of end-stage renal disease. Antihypertensive agents are used clinically to inhibit the progression of CKD, but cannot prevent eventual renal failure. This study investigated the effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, in rats suffering from CKD induced by 5/6 nephrectomy. After development of renal insufficiency, the rats were treated with Tanshinone IIA (10 mg/kg) for 8 weeks. Serum creatinine, angiotensin II (Ang II), transforming growth factor β1 (TGF-β1) and collagen IV levels were significantly reduced in Tanshinone IIA treated rats compared with a control group. In addition, Tanshinone IIA suppressed increases in urinary protein excretion in CKD rats. These findings suggest that chronic oral administration of Tanshinone IIA can improve renal dysfunction associated with CKD.

Topics: Abietanes; Administration, Oral; Angiotensin II; Animals; Collagen Type IV; Creatinine; Disease Models, Animal; Drugs, Chinese Herbal; Kidney; Male; Phenanthrenes; Proteinuria; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Salvia miltiorrhiza; Transforming Growth Factor beta1