Gu L.,Mount Sinai School of Medicine |
Gu L.,Molecular Cell Laboratory for Kidney Disease |
Dai Y.,Mount Sinai School of Medicine |
Dai Y.,Shanghai JiaoTong University |
And 7 more authors.
AIDS | Year: 2013
Objective: HIV-1 gene expression in kidney epithelial cells is thought to be responsible for the pathogenesis of HIV-1-associated nephropathy (HIVAN). Signal transducer and activator of transcription (STAT) 3 signaling is activated in podocytes of patients with HIVAN and drives the dedifferentiation and proliferation of podocytes in culture. We confirm here that deletion of podocyte STAT3 is sufficient to mitigate the glomerular as well as tubulointerstitial findings of HIVAN. Methods: To demonstrate the functional role of podocyte STAT3 in the pathogenesis of HIVAN we compared the development of HIVAN in Tg26 HIV-transgenic mice with and without deletion of STAT3 in the podocyte. Results: Tg26 mice with podocyte-specific STAT3 deletion developed significantly less weight loss, albuminuria, and renal function impairment compared to Tg26 mice without STAT3 deletion. Tg26 mice with podocyte STAT3 deletion also had significantly less glomerular collapse, sclerosis, epithelial cell hyperplasia, podocyte dedifferentiation, and proinflammatory STAT3 target gene expression; and tubulointerstitial changes of HIVAN, including tubular atrophy, degeneration, apoptosis, and lymphocyte infiltration, were also significantly reduced compared to Tg26 mice without STAT3 deletion. Conclusion: Development of glomerular as well as tubulointerstitial injuries in the Tg26 HIVAN model is dependent on podocyte STAT3 expression. Inhibition of STAT3 could be a potential adjunctive therapy for the treatment of HIVAN. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source
Mou S.,Molecular Cell Laboratory for Kidney Disease |
Wang Q.,Molecular Cell Laboratory for Kidney Disease |
Liu J.,Molecular Cell Laboratory for Kidney Disease |
Che X.,Molecular Cell Laboratory for Kidney Disease |
And 4 more authors.
Diabetes Research and Clinical Practice | Year: 2010
It is important to differentiate proteinuria from non-diabetic renal diseases (NDRD) or diabetic nephropathy in diabetic patients. The purpose of our study was to evaluate the prevalence of NDRD. A retrospective analysis was performed on diabetic patients who had undergone renal biopsy during a 6-year period. Our study revealed a high prevalence of NDRD in the diabetic population. Sixty-nine patients were investigated, 52.2% were diagnosed as NDRD and 47.8% as DN. Focal segmental glomerulosclerosis was the most common lesion found in patients with NDRD. We found a relationship between DN and fasting blood glucose level, systolic blood pressure, diastolic blood pressure, LVMI, intima-media thickening (IMT), and the presence of carotid plaques. Patients with NDRD had a lower incidence of diabetic retinopathy (DR). The absence of DR to differentiate NDRD had a sensitivity of 72.7%, a specificity 91.7%, and an ROC = 0.822. Fasting blood glucose level had a sensitivity and specificity of 93.9% and 75%, respectively. Similarly, the use of IMT had sensitivity and specificity of 90% and 75.8%, respectively. In this study, we determined that the absence of DR, a lower fasting blood glucose level, and IMT is useful in differentiating NDRD from DN in diabetic patients with overt proteinuria. © 2009 Elsevier Ireland Ltd. All rights reserved. Source