Lei-shi Li

Rhein reverses the diabetic phenotype of mesangial cells over-expressing the glucose transporter (GLUT1) by inhibiting the hexosamine pathway

Background and purpose: Rhein, an anthraquinone compound isolated from rhubarb, has been proved effective in treatment of experimental diabetic nephropathy (DN). To explore the mechanism of its therapeutic effect on DN, rhein was tested for its effect on the hexosamine pathway.

Enhanced Expression of ANGPTL2 in the Microvascular Lesions of Diabetic Glomerulopathy

Background: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. However, the underlying mechanisms remain unclear. We studied the expression characteristics of angiopoietin-like 2 (ANGPTL2), a novel DN-associated growth factor identified in our previous gene chip screening. Methods: Glomeruli were microdissected from renal biopsies from 24 patients with DN and 8 donor controls. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with clinical and pathological indices of glomerular injury. Results: Consistent with the results of the gene chip experiment, abundant expression of ANGPTL2 was found more frequently in diabetic glomeruli as compared to donor controls (95 vs. 38%, χ2 = 15.9, p < 0.01). ANGPTL2 mRNA upregulation was more prominent in glomeruli with less microaneurysm (22 vs. 66%, p < 0.05), inflammatory influx (6 vs. 50%, p < 0.05) or endothelial foam cell formation (11 vs. 53%, p < 0.05). Immunostaining revealed an upregulation of ANGPTL2 protein in hypertrophied diabetic glomeruli, mainly distributed in podocytes, which were supposed to be the origin of ANGPTL2. Conclusion: The upregulation of ANGPTL2 in diabetic glomerulopathy shows a close relationship to abnormal microvasculature and endothelial inflammation. ANGPTL2 may play an important role in the pathogenesis of diabetic glomerulopathy.

Mast cell infiltration associated with tubulointerstitial fibrosis in chronic Aristolochic Acid Nephropathy.

Aristolochic Acid Nephropathy (AAN) is regarded as a kind of toxic nephropathy caused by the formation of DNA- aristolochic acid adducts in renal parenchymal cells. However, the underlying mechanisms driving the progression of renal interstitial fibrosis in AAN still remains unclear. This study aims to elucidate the role of some immunological factors, especially mast cells (MCs), in the pathogenesis of AAN. Sixteen patients with AAN were enrolled in this study, including five acute and 11 chronic AAN. Monoclonal antibodies against human tryptase, alpha smooth muscle actin (α-SMA), and CD68 were applied on serial sections, which were further counterstained with Periodic Acid-Schiff. It was found that massive tryptase-positive MCs were observed in the fibrotic areas in chronic AAN, especially around thickened tubular basement membranes where myofibroblasts accumulated too. In contrast, MCs infiltrated to a less extent in acute AAN, and were barely found in normal control kidneys. In chronic AAN, the number of MCs in the tubulointerstitium was positively correlated with the degree of renal fibrosis (r=0.64, P<0.05), but not with serum creatinine levels. Meanwhile, the recruitment of MCs into the renal interstitium is accompanied with local proliferation of myofibroblasts. Macrophages were not abundant, neither in acute nor in chronic AAN. Our findings show for the first time that mast cell infiltration seems to be associated with the progression of fibrosis in the renal tubulointerstitium in chronic AAN.