The Study of Angptl4-Modulated Podocyte Injury in IgA Nephropathy.

Sha Jia,Xiaofeng Peng,Shi Feng,Ying Zhang,Meng Li,Yucheng Wang,Xiujin Shen,Cuili Wang,Jianghua Chen,Qin Zhou,Ludan Liang,Pingping Ren,Hong Jiang

doi:10.3389/fphys.2020.575722

Abstract

BackgroundIncreasing 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.MethodsPlasma 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.ResultsThirty-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.ConclusionOur 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.

Highlights

Immunoglobulin A nephropathy (IgAN), which is characterized by galactose-deficient IgA deposits in the glomerular mesangium, is the most prevalent type of glomerulonephritis worldwide (Suzuki et al, 2011; Wyatt and Julian, 2013)
The IgAN group was further divided into two groups according to electron microscopy results: one group consisted of 37 patients with foot process fusion, and the other group consisted of 34 patients without foot process fusion
The patients in the IgAN with and without podocyte injury groups presented with a mean serum creatinine level of 187.22 ± 20.61 and 95.94 ± 5.97 μmol/L, and a mean serum albumin level of 35.20 ± 0.98 and 37.89 ± 1.25 g/L, respectively (P < 0.05) compared with the healthy controls)

Summary

Introduction

Immunoglobulin A nephropathy (IgAN), which is characterized by galactose-deficient IgA deposits in the glomerular mesangium, is the most prevalent type of glomerulonephritis worldwide (Suzuki et al, 2011; Wyatt and Julian, 2013). IgAN is one of the major causes of end-stage renal disease (ESRD), proteinuria, and hypertension. Podocytes possess numerous foot processes, surround glomerular capillaries, and serve as the last barrier to renal filtration (Greka and Mundel, 2012). Foot process effacement is a hallmark of podocyte injury, which leads to proteinuria and glomerulosclerosis (Lemley et al, 2002; Hara et al, 2007). Increasing evidence shows that Angptl affects proteinuria in podocytes injured kidney disease, whether there is a relationship between Angptl and IgA nephropathy (IgAN) has not been studied yet

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Conclusion