Thiazolidinediones, synthetic ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), are reported to have direct beneficial effects on diabetic nephropathy without lowering blood glucose levels in human and rat. We hypothesized these effects of thiazolidinediones might be derived from PPARgamma activation of kidney cells, and we examined the expression of PPARgamma and the effect of PPARgamma agonists, troglitazone and 15-deoxy-delta-prostaglandin J2 (15d-PGJ2), on the proliferation and differentiation in rat mesangial cells. A single band of mRNA of PPARgamma with a predicted size was detected in reverse transcription-polymerase chain reaction products (RT-PCR) using established PCR probes of PPARgamma. PPARgamma protein in rat mesangial cells was identified as PPARgamma1 by a Western blot. In a gel mobility shift assay to determine a binding activity of PPARgamma, the nuclear protein from rat mesangial cells bound to a (32)P-labeled oligonucleotide probe, including PPAR response elements. A synthetic and a natural ligand of PPARgamma, troglitazone and 15d-PGJ2, decreased thymidine incorporation in a dose dependent manner. After 7 days incubation with troglitazone and 15d-PGJ2, alpha-smooth muscle actin expression, a marker of mesangial cell de-differentiation, was decreased significantly compared to that of control. These results indicate that PPARgamma1 is expressing in rat mesangial cells, and PPARgamma1 activation with its agonists modulates the proliferation and differentiation of cultured rat mesangial cells.
The CACI was a significant independent predictor of prognosis and compliance for postoperative adjuvant chemotherapy in the resected pancreatic cancer.
The incidence of HJ stenosis was 8.0%. Close attention would be needed especially for patients at high risk of HJ stenosis, such as high BMI or absence of preoperative biliary stenting.
We previously reported that sodium-dependent glucose uptake is present in bovine retinal pericytes and that phlorizin normalizes its glucose consumption under high glucose conditions. To clarify the effect of phlorizin on morphological and functional change of retinal pericytes under high glucose conditions, retinal pericytes were incubated in media with 5 mM glucose, 30 mM glucose, and 30 mM glucose plus 0.2 mM phlorizin for 7 days. The diameter of cells in the concentrations of glucose more than 10 mM were significantly larger than those in 5 mM glucose and 30 mM glucose plus phlorizin. Glucose, sorbitol and fructose contents of the cells in 30 mM glucose were significantly increased compared with those in 5 mM glucose, and were normalized by phlorizin. Thymidine uptake in the concentrations of glucose more than 20 mM was significantly decreased compared with that in 5 mM glucose. Myoinositol uptake, and DNA in 30 mM glucose were significantly reduced, and were normalized with phlorizin. Myoinositol content in 30 mM glucose was the same as that in 5 mM glucose, but was significantly decreased by phlorizin. The ratios of glucose to sorbitol or fructose in 30 mM glucose were significantly decreased, compared with those in 5 mM glucose and 30 mM glucose plus phlorizin. Therefore, the cellular enlargement and decreased DNA synthesis in cultured bovine retinal pericytes with abnormal glucose metabolism under high glucose conditions are attenuated by phlorizin, independent of the cellular myoinositol content.
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