Background: Rapidly progressive glomerulonephritis (RPGN) is caused by various diseases process, thereby resulting in extensive crescent formation, which could lead to a rapid loss of kidney function. The molecular pathogenesis of RPGN remains largely unknown and requires clarification. The weighted gene co-expression network analysis (WGCNA) is a powerful bioinformatics tool to identify meaningful molecules in diseases. Methods: The dataset of GSE104948, which contains 22 RPGN and 18 normal samples, was obtained from Gene Expression Omnibus database. After data pre-processing, the WGCNA was performed to successfully cluster several significant modules. The most significant module was selected for further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Visualization of network and screening of hub genes were performed by using Cytoscape software. Results: A total of 11 modules were clustered by WGCNA, and the most significant module-turquoise module was selected. As discovered via GO enrichment and KEGG pathway analysis, the turquoise module was mainly associated with neutrophil activation and degranulation. After visualization and calculation for the network, the PYCARD gene has higher relationship score in 2 clusters, namely, neutrophil activation and degranulation. In accordance with the literature review, the hub gene could be closely related to the inflammation response and could act as the potential therapeutic targets in RPGN. Conclusions: WGCNA in RPGN expression profiling was used for the first time in this paper. A novel hub gene closely associated with RPGN was screened out, thereby providing the brand-new molecular candidate for RPGN.

1.
Couser WG: Rapidly progressive glomerulonephritis – classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis 1988; 11: 449–464.
2.
Henique C, Papista C, Guyonnet L, Lenoir O, Tharaux PL: Update on crescentic glomerulonephritis. Semin Immunopathol 2014; 36: 479–490.
3.
Chen S, Tang Z, Xiang H, Li X, Chen H, Zhang H, Hu W, Zeng C, Liu Z: Etiology and outcome of crescentic glomerulonephritis from a single center in China: a 10-year review. Am J Kidney Dis 2016; 67: 376–383.
4.
Jennette JC: Rapidly progressive crescentic glomerulonephritis. Kidney Int 2003; 63: 1164–1177.
5.
Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK, Ellis E, Lovell H, Warady B, Gunwar S, Chonko AM, Artero M, Vincenti F: Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996; 334: 878–883.
6.
Henique C, Bollee G, Lenoir O, Dhaun N, Camus M, Chipont A, Flosseau K, Mandet C, Yamamoto M, Karras A, Thervet E, Bruneval P, Nochy D, Mesnard L, Tharaux PL: Nuclear factor erythroid 2-related factor 2 drives podocyte-specific expression of peroxisome proliferator-activated receptor γ essential for resistance to crescentic GN. J Am Soc Nephrol 2016; 27: 172–188.
7.
Bollee G, Flamant M, Schordan S, Fligny C, Rumpel E, Milon M, Schordan E, Sabaa N, Vandermeersch S, Galaup A, Rodenas A, Casal I, Sunnarborg SW, Salant DJ, Kopp JB, Threadgill DW, Quaggin SE, Dussaule JC, Germain S, Mesnard L, Endlich K, Boucheix C, Belenfant X, Callard P, Endlich N, Tharaux PL: Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis. Nat Med 2011; 17: 1242–1250.
8.
Ding M, Cui S, Li C, Jothy S, Haase V, Steer BM, Marsden PA, Pippin J, Shankland S, Rastaldi MP, Cohen CD, Kretzler M, Quaggin SE: Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice. Nat Med 2006; 12: 1081–1087.
9.
Wada T, Furuichi K, Segawa-Takaeda C, Shimizu M, Sakai N, Takeda SI, Takasawa K, Kida H, Kobayashi KI, Mukaida N, Ohmoto Y, Matsushima K, Yokoyama H: MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis. Kidney Int 1999; 56: 995–1003.
10.
Taekema-Roelvink ME, Van Kooten C, Heemskerk E, Schroeijers W, Daha MR: Proteinase 3 interacts with a 111-kD membrane molecule of human umbilical vein endothelial cells. J Am Soc Nephrol 2000; 11: 640–648.
11.
Kurosawa S, Esmon CT, Stearns-Kurosawa DJ: The soluble endothelial protein C receptor binds to activated neutrophils: involvement of proteinase-3 and CD11b/CD18. J Immunol 2000; 165: 4697–4703.
12.
Ciavatta DJ, Yang J, Preston GA, Badhwar AK, Xiao H, Hewins P, Nester CM, Pendergraft WF 3rd, Magnuson TR, Jennette JC, Falk RJ: Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis. J Clin Invest 2010; 120: 3209–3219.
13.
Langfelder P, Horvath S: WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 2008; 9: 559.
14.
Guo L, Zhang K, Bing Z: Application of a co-expression network for the analysis of aggressive and non-aggressive breast cancer cell lines to predict the clinical outcome of patients. Mol Med Rep 2017; 16: 7967–7978.
15.
Giulietti M, Occhipinti G, Principato G, Piva F: Weighted gene co-expression network analysis reveals key genes involved in pancreatic ductal adenocarcinoma development. Cell Oncol (Dordr) 2016; 39: 379–388.
16.
Wang B, He L, Miao W, Wu G, Jiang H, Wu Y, Qu J, Li M: Identification of key genes associated with Schmid-type metaphyseal chondrodysplasia based on microarray data. Int J Mol Med 2017; 39: 1428–1436.
17.
Gautier L, Cope L, Bolstad BM, Irizarry RA: Affy – analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 2004; 20: 307–315.
18.
Forero DA, Guio-Vega GP, Gonzalez-Giraldo Y: A comprehensive regional analysis of genome-wide expression profiles for major depressive disorder. J Affect Disord 2017; 218: 86–92.
19.
Yu G, Wang LG, Han Y, He QY: ClusterProfiler: an R package for comparing biological themes among gene clusters. Omics 2012; 16: 284–287.
20.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13: 2498–2504.
21.
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY: CytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014; 8(suppl 4):S11.
22.
Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES: The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem 2002; 277: 21119–21122.
23.
Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK, Vos MR, Schroder GF, Fitzgerald KA, Wu H, Egelman EH: Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 2014; 156: 1193–1206.
24.
Dowds TA, Masumoto J, Zhu L, Inohara N, Nunez G: Cryopyrin-induced interleukin 1beta secretion in monocytic cells: enhanced activity of disease-associated mutants and requirement for ASC. J Biol Chem 2004; 279: 21924–21928.
25.
Satoh T, Kambe N, Matsue H: NLRP3 activation induces ASC-dependent programmed necrotic cell death, which leads to neutrophilic inflammation. Cell Death Dis 2013; 4: e644.
26.
Sarkar A, Duncan M, Hart J, Hertlein E, Guttridge DC, Wewers MD: ASC Directs NF- kappaB activation by regulating receptor interacting protein-2 (RIP2) caspase-1 interactions. J Immunol 2006; 176: 4979–4986.
27.
Mhyre AJ, Marcondes AM, Spaulding EY, Deeg HJ: Stroma-dependent apoptosis in clonal hematopoietic precursors correlates with expression of PYCARD. Blood 2009; 113: 649–658.
28.
Hasegawa M, Kawase K, Inohara N, Imamura R, Yeh WC, Kinoshita T, Suda T: Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type II cells. Oncogene 2007; 26: 1748–1756.
29.
Motani K, Kushiyama H, Imamura R, Kinoshita T, Nishiuchi T, Suda T: Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity. J Biol Chem 2011; 286: 33963–33972.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.