Year: 2017
Type: conference-abstract
Abstract: INTRODUCTION AND AIMS: Diabetic Nephropathy (DN) is one of the most serious and harmful complications caused by diabetes mellitus. Our previous findings have shown that the transcription factor C/EBPα (CCAAT/enhancer-binding protein α) plays a role in improving tubulointerstitial fibrosis and glucose and lipid metabolism. The purpose of this study was to investigate the effect and mechanism of C/EBPα in DN, so as to promote a new way for clinical diagnosis and treatment of DN. METHODS: Wild type (WT) mice, podocyte-specific C/EBPα-null heterozygous (podocin-C/EBPαf/+) and homozygous (podocin-C/EBPαf/f) mice were fed with 45%high-fat-diet (HFD) for 5 months, and then were administrated a low dose of streptozotocin (STZ 100g/kg) by intraperitoneal injection. The DN model was successfully constructed after two weeks. Physiological and biochemical indexes of blood and urine were tested, and the morphologic changes of renal tissues were evaluated by HE and Masson staining. RESULTS: The fasting and random blood glucose and oral glucose tolerance test (OGTT) demonstrated that all the blood glucose and insulin resistance of HFD combined with STZ treated mice increased significantly and maintain stability, indicating the success of type 2 diabetes mellitus model. In addition, the 24h urine volume and the ratio of urinary albumin and creatinine (ACR) of podocin-C/EBPαf/+ and podocin-C/EBPαf/f mice was significantly higher than that of WT mice (P<0.01). Although the 24h urine volume of podocin-C/EBPαf/f mice showed no significant difference with the podocin-C/EBPαf/+ mice, the ACR of podocin-C/EBPαf/f mice was significantly higher than that of podocin-C/EBPαf/+ mice (P<0.01). HE and Masson staining of kidney illustrated that compared to the HFD WT mice, podocin-C/EBPαf/f mice showed significantly expanded mesangial area with mesangial cells proliferation and mesangial matrix accumulation, and basement membrane thickening as the glomerular pathological changes, while in tubulointerstitium with obvious focal renal tubular expansion and infiltration of lymphocytes, which suggested C/EBPα null in podocytes exacerbated the inflammation in DN. CONCLUSIONS: Podocyte specific C/EBPα null can deteriorate renal impairment of DN, and C/EBPα may protect against DN through inflammation inhibition and metabolic regulation.
Authors: Zhou Fangfang, Zhang Liwen, Liu Jian, Ying Ji, Zhong Fang, Wang Weiming, Chen Nan
Institutions: Shanghai Jiao Tong University, Ruijin Hospital
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2616996776