Sha Jia1,2,3,4,5,6, Xiaofeng Peng1,2,3,4,5, Ludan Liang1,2,3,4,5, Ying Zhang1,2,3,4,5, Meng Li1,2,3,4,5, Qin Zhou1,2,3,4,5, Xiujin Shen1,2,3,4,5, Yucheng Wang1,2,3,4,5, Cuili Wang1,2,3,4,5, Shi Feng1,2,3,4,5, Jianghua Chen1,2,3,4,5, Pingping Ren1,2,3,4,5, Hong Jiang1,2,3,4,5. 1. Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 2. Key Laboratory of Nephropathy, Hangzhou, China. 3. Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Hangzhou, China. 4. Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Beijing, China. 5. Institute of Nephropathy, Zhejiang University, Hangzhou, China. 6. Dongyang Women & Children Hospital, Dongyang, China.
Abstract
BACKGROUND: Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet. METHODS: Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed. RESULTS: Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio. CONCLUSION: Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.
BACKGROUND: Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet. METHODS: Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed. RESULTS: Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio. CONCLUSION: Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.
Authors: Lionel C Clement; Camille Macé; Carmen Avila-Casado; Jaap A Joles; Sander Kersten; Sumant S Chugh Journal: Nat Med Date: 2013-12-08 Impact factor: 53.440
Authors: Hong Jiang; Eric Schiffer; Zhangfa Song; Jianwei Wang; Petra Zürbig; Kathrin Thedieck; Suzette Moes; Heike Bantel; Nadja Saal; Justyna Jantos; Meiken Brecht; Paul Jenö; Michael N Hall; Klaus Hager; Michael P Manns; Hartmut Hecker; Arnold Ganser; Konstanze Döhner; Andrzej Bartke; Christoph Meissner; Harald Mischak; Zhenyu Ju; K Lenhard Rudolph Journal: Proc Natl Acad Sci U S A Date: 2008-08-11 Impact factor: 11.205