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102. Diagnostic utility of genetic testing in patients undergoing renal biopsy

Author

Benson, Katherine A., primary, Murray, Susan L., additional, Doyle, Ross, additional, Doyle, Brendan, additional, Dorman, Anthony M., additional, Sadlier, Denise, additional, Brennan, Eoin, additional, Large, Margaret, additional, Cavalleri, Gianpiero L., additional, Godson, Catherine, additional, and Conlon, Peter J., additional

Published
2020
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103. Characterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney disease

Author

Nair, Meera, primary, Martin, William P, additional, Zhernovkov, Vadim, additional, Elliott, Jessie A, additional, Fearon, Naomi, additional, Eckhardt, Hans, additional, McCormack, Janet, additional, Godson, Catherine, additional, Brennan, Eoin Patrick, additional, Fandriks, Lars, additional, Docherty, Neil G, additional, and le Roux, Carel W, additional

Published
2020
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123. The Atlas of Inflammation-Resolution (AIR)

Author

Serhan, Charles N., primary, Gupta, Shailendra, additional, Perretti, Mauro, additional, Godson, Catherine, additional, Brennan, Eoin, additional, Li, Yongsheng, additional, Soehnlein, Oliver, additional, Shimizu, Takao, additional, Werz, Oliver, additional, Chiurchiù, Valerio, additional, Azzi, Angelo, additional, Dubourdeau, Marc, additional, Gupta, Suchi Smita, additional, Schopohl, Patrick, additional, Hoch, Matti, additional, Gjorgevikj, Dragana, additional, Khan, Faiz M., additional, Brauer, David, additional, Tripathi, Anurag, additional, Cesnulevicius, Konstantin, additional, Lescheid, David, additional, Schultz, Myron, additional, Repsilber, Dirk, additional, Kruse, Robert, additional, Sala, Angelo, additional, Haeggström, Jesper Z., additional, Levy, Bruce D., additional, Filep, János G., additional, and Wolkenhauer, Olaf, additional

Published
2020
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126. Contributors

Author

Agarwal, Anupam, Ashley, Sophie L., Asthana, Amish, Atala, Anthony, Babickova, Janka, Baird, David P., Basile, David P., Bedzow, Ira, Bhattacharya, Rohan, Blank, Ulrich, Bonventre, Joseph V., Borradaile, Nica M., Celikoyar, Selin, Charles, Nicolas, Cheung, Matthew D., Choi, Hoon Young, Crunk, Amanda E., Daugas, Eric, Dekel, Benjamin, Demaria, Marco, Diegisser, Danielle, Ding, Feng, Dirice, Ercument, Doyle, Ross, Ebert, Thomas, Erman, Elise N., Ferenbach, David A., Fogo, Agnes B., Francipane, Maria Giovanna, George, James F., Godson, Catherine, Golestaneh, Ladan, Goligorsky, Michael S., Haber, Dylan, He, John Cijiang, Heller, Daniel A., Holmes, Jordan A., Hukriede, Neil A., Hunsberger, Joshua, Izpisua Belmonte, Juan Carlos, Jaimes, Edgar A., Ji, Jing, Kahraman, Sevim, Kalejaiye, Titilola D., Kapadia, Chintan, Kretzler, Matthias, La Pointe, Catherine, Lasagni, Laura, Lee, Jason J., Lee, Kyung, Lerman, Lilach O., Li, Li, Li, Xuezhu, Mahler, Gretchen J., Marino, Domenica Ida, Mazzinghi, Benedetta, Melk, A., Muir, Sean, Musah, Samira, Nath, Meryl C., Nehme, Jamil, Neugarten, Joel, Nicolas, Paola, Okusa, Mark D., Orlando, Giuseppe, Osafune, Kenji, Park, Hyeong Cheon, Pickering, J. Geoffrey, Pleniceanu, Oren, Przepiorski, Aneta, Rabadi, May M., Ratliff, Brian B., Romagnani, Paola, Schaub, Jennifer A., Schmitt, R., Somara, Sita, Stenvinkel, Peter, Varela-Eirin, Marta, Williams, Ryan M., Wilson, Rachel B., Woolf, Adrian S., Xia, Yun, Yang, Hai-Chun, Yang, Li, Yoder, Mervin C., Zhang, Stephanie, Zhang, Yuanyuan, and Zhu, Xiang Yang

Published
2022
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130. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

Author

Salem, Rany M., Todd, Jennifer N., Sandholm, Niina, Cole, Joanne B., Chen, Wei-Min, Andrews, Darrell, Pezzolesi, Marcus G., McKeigue, Paul M., Hiraki, Linda T., Qiu, Chengxiang, Nair, Viji, Di Liao, Chen, Cao, Jing Jing, Valo, Erkka, Onengut-Gumuscu, Suna, Smiles, Adam M., McGurnaghan, Stuart J., Haukka, Jani K., Harjutsalo, Valma, Brennan, Eoin P., van Zuydam, Natalie, Ahlqvist, Emma, Doyle, Ross, Ahluwalia, Tarunveer S., Lajer, Maria, Hughes, Maria F., Park, Jihwan, Skupien, Jan, Spiliopoulou, Athina, Liu, Andrew, Menon, Rajasree, Boustany-Kari, Carine M., Kang, Hyun M., Nelson, Robert G., Klein, Ronald, Klein, Barbara E., Lee, Kristine E., Gao, Xiaoyu, Mauer, Michael, Maestroni, Silvia, Caramori, Maria Luiza, de Boer, Ian H., Miller, Rachel G., Guo, Jingchuan, Boright, Andrew P., Tregouet, David, Gyorgy, Beata, Snell-Bergeon, Janet K., Maahs, David M., Bull, Shelley B., Canty, Angelo J., Palmer, Colin N. A., Stechemesser, Lars, Paulweber, Bernhard, Weitgasser, Raimund, Sokolovska, Jelizaveta, Rovite, Vita, Pirags, Valdis, Prakapiene, Edita, Radzeviciene, Lina, Verkauskiene, Rasa, Panduru, Nicolae Mircea, Groop, Leif C., McCarthy, Mark, I, Gu, Harvest F., Möllsten, Anna, Falhammar, Henrik, Brismar, Kerstin, Martin, Finian, Rossing, Peter, Costacou, Tina, Zerbini, Gianpaolo, Marre, Michel, Hadjadj, Samy, McKnight, Amy J., Forsblom, Carol, McKay, Gareth, Godson, Catherine, Maxwell, A. Peter, Kretzler, Matthias, Susztak, Katalin, Colhoun, Helen M., Krolewski, Andrzej, Paterson, Andrew D., Groop, Per-Henrik, Rich, Stephen S., Hirschhorn, Joel N., Florez, Jose C., Salem, Rany M., Todd, Jennifer N., Sandholm, Niina, Cole, Joanne B., Chen, Wei-Min, Andrews, Darrell, Pezzolesi, Marcus G., McKeigue, Paul M., Hiraki, Linda T., Qiu, Chengxiang, Nair, Viji, Di Liao, Chen, Cao, Jing Jing, Valo, Erkka, Onengut-Gumuscu, Suna, Smiles, Adam M., McGurnaghan, Stuart J., Haukka, Jani K., Harjutsalo, Valma, Brennan, Eoin P., van Zuydam, Natalie, Ahlqvist, Emma, Doyle, Ross, Ahluwalia, Tarunveer S., Lajer, Maria, Hughes, Maria F., Park, Jihwan, Skupien, Jan, Spiliopoulou, Athina, Liu, Andrew, Menon, Rajasree, Boustany-Kari, Carine M., Kang, Hyun M., Nelson, Robert G., Klein, Ronald, Klein, Barbara E., Lee, Kristine E., Gao, Xiaoyu, Mauer, Michael, Maestroni, Silvia, Caramori, Maria Luiza, de Boer, Ian H., Miller, Rachel G., Guo, Jingchuan, Boright, Andrew P., Tregouet, David, Gyorgy, Beata, Snell-Bergeon, Janet K., Maahs, David M., Bull, Shelley B., Canty, Angelo J., Palmer, Colin N. A., Stechemesser, Lars, Paulweber, Bernhard, Weitgasser, Raimund, Sokolovska, Jelizaveta, Rovite, Vita, Pirags, Valdis, Prakapiene, Edita, Radzeviciene, Lina, Verkauskiene, Rasa, Panduru, Nicolae Mircea, Groop, Leif C., McCarthy, Mark, I, Gu, Harvest F., Möllsten, Anna, Falhammar, Henrik, Brismar, Kerstin, Martin, Finian, Rossing, Peter, Costacou, Tina, Zerbini, Gianpaolo, Marre, Michel, Hadjadj, Samy, McKnight, Amy J., Forsblom, Carol, McKay, Gareth, Godson, Catherine, Maxwell, A. Peter, Kretzler, Matthias, Susztak, Katalin, Colhoun, Helen M., Krolewski, Andrzej, Paterson, Andrew D., Groop, Per-Henrik, Rich, Stephen S., Hirschhorn, Joel N., and Florez, Jose C.

Abstract

Background: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. Methods: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. Results: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1). Conclusions: The 16 diabetic kidney disease–associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.

Published
2019
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133. Pro-resolving lipid mediators: regulators of inflammation, metabolism and kidney function

Author

Brennan, Eoin, Kantharidis, Phillip, Cooper, Mark E., and Godson, Catherine

Abstract

Obesity, diabetes mellitus, hypertension and cardiovascular disease are risk factors for chronic kidney disease (CKD) and kidney failure. Chronic, low-grade inflammation is recognized as a major pathogenic mechanism that underlies the association between CKD and obesity, impaired glucose tolerance, insulin resistance and diabetes, through interaction between resident and/or circulating immune cells with parenchymal cells. Thus, considerable interest exists in approaches that target inflammation as a strategy to manage CKD. The initial phase of the inflammatory response to injury or metabolic dysfunction reflects the release of pro-inflammatory mediators including peptides, lipids and cytokines, and the recruitment of leukocytes. In self-limiting inflammation, the evolving inflammatory response is coupled to distinct processes that promote the resolution of inflammation and restore homeostasis. The discovery of endogenously generated lipid mediators — specialized pro-resolving lipid mediators and branched fatty acid esters of hydroxy fatty acids — which promote the resolution of inflammation and attenuate the microvascular and macrovascular complications of obesity and diabetes mellitus highlights novel opportunities for potential therapeutic intervention through the targeting of pro-resolution, rather than anti-inflammatory pathways.

Published
2021
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135. Unravelling the transcriptional responses of TGF‐β: Smad3 and EZH2 constitute a regulatory switch that controls neuroretinal epithelial cell fate specification

Author

Andrews, Darrell, primary, Oliviero, Giorgio, additional, De Chiara, Letizia, additional, Watson, Ariane, additional, Rochford, Emily, additional, Wynne, Kieran, additional, Kennedy, Ciaran, additional, Clerkin, Shane, additional, Doyle, Benjamin, additional, Godson, Catherine, additional, Connell, Paul, additional, O'Brien, Colm, additional, Cagney, Gerard, additional, and Crean, John, additional

Published
2019
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136. Asymmetric synthesis and biological evaluation of imidazole- and oxazole-containing synthetic lipoxin A4 mimetics (sLXms)

Author

de Gaetano, Monica, primary, Butler, Eibhlín, additional, Gahan, Kevin, additional, Zanetti, Andrea, additional, Marai, Mariam, additional, Chen, Jianmin, additional, Cacace, Antonino, additional, Hams, Emily, additional, Maingot, Catherine, additional, McLoughlin, Alisha, additional, Brennan, Eoin, additional, Leroy, Xavier, additional, Loscher, Christine E., additional, Fallon, Padraic, additional, Perretti, Mauro, additional, Godson, Catherine, additional, and Guiry, Patrick J., additional

Published
2019
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140. Lipoxins Protect Against Inflammation in Diabetes-Associated Atherosclerosis

Author

Brennan, Eoin P., primary, Mohan, Muthukumar, additional, McClelland, Aaron, additional, de Gaetano, Monica, additional, Tikellis, Christos, additional, Marai, Mariam, additional, Crean, Daniel, additional, Dai, Aozhi, additional, Beuscart, Ophelie, additional, Derouiche, Sinda, additional, Gray, Stephen P., additional, Pickering, Raelene, additional, Tan, Sih Min, additional, Godson-Treacy, Molly, additional, Sheehan, Stephen, additional, Dowdall, Joseph F., additional, Barry, Mary, additional, Belton, Orina, additional, Ali-Shah, Syed Tasadaque, additional, Guiry, Patrick J., additional, Jandeleit-Dahm, Karin, additional, Cooper, Mark E., additional, Godson, Catherine, additional, and Kantharidis, Phillip, additional

Published
2018
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141. Melatonin receptors step into the light: cloning and classification of subtypes

Author

Reppert, Steven M., Weaver, David R., and Godson, Catherine

Subjects
Melatonin -- Research, G proteins -- Research, Biological sciences, Chemistry, Pharmaceuticals and cosmetics industries
Abstract

Melatonin is a hormone secreted by the pineal gland in response to a variety of biological stimuli. Recent studies using 2-[125]iodomelatonin have identified high-affinity melatonin receptors in several vertebrate species. The G protein-coupled melatonin receptors were the first melatonin receptors identified using expression cloning. The second cloned receptor was designated the Mel1b receptor and Mel1a receptor as the third cloned receptor. Molecular and genetic studies have shown that these three receptor subtypes have a similar gene structure.

Published
1996

143. Lipoxins regulate the early growth response-1 network and reverse diabetic Kidney disease

Author

Brennan, Eoin P., Mohan, Muthukumar, McClelland, Aaron, Tikellis, Christos, Ziemann, Mark, Kaspi, Antony, Gray, Stephen P., Pickering, Raelene, Tan, Sih Min, Ali-Shah, Syed Tasadaque, Guiry, Patrick J., El-Osta, Assam, Jandeleit-Dahm, Karin, Cooper, Mark E., Godson, Catherine, Kantharidis, Phillip, Brennan, Eoin P., Mohan, Muthukumar, McClelland, Aaron, Tikellis, Christos, Ziemann, Mark, Kaspi, Antony, Gray, Stephen P., Pickering, Raelene, Tan, Sih Min, Ali-Shah, Syed Tasadaque, Guiry, Patrick J., El-Osta, Assam, Jandeleit-Dahm, Karin, Cooper, Mark E., Godson, Catherine, and Kantharidis, Phillip

Published
2018

146. REST is a hypoxia-responsive transcriptional repressor

Author

Cavadas, Miguel A. S., Mesnieres, Marion, Crifo, Bianca, Manresa, Mario C., Selfridge, Andrew C., Keogh, Ciara E., Fabian, Zsolt, Scholz, Carsten C., Nolan, Karen A., Rocha, Liliane M. A., Tambuwala, Murtaza M., Brown, Stuart, Wdowicz, Anita, Corbett, Danielle, Murphy, Keith J., Godson, Catherine, Cummins, Eoin P., Taylor, Cormac T., Cheong, Alex, University of Zurich, and Cheong, Alex

Subjects
1000 Multidisciplinary, HEK293, REST, Transcriptional regulatory elements, Gene silencing, 610 Medicine & health, A300, Hypoxia-inducible factor, 10052 Institute of Physiology, Hypoxia-responsive, 10076 Center for Integrative Human Physiology, HIF, 570 Life sciences, biology, Hypoxia
Abstract

Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia. Science Foundation Ireland grant: (06/CE/B1129).

Published
2016

147. Lipoxins Regulate the Early Growth Response–1 Network and Reverse Diabetic Kidney Disease

Author

Brennan, Eoin P., primary, Mohan, Muthukumar, additional, McClelland, Aaron, additional, Tikellis, Christos, additional, Ziemann, Mark, additional, Kaspi, Antony, additional, Gray, Stephen P., additional, Pickering, Raelene, additional, Tan, Sih Min, additional, Ali-Shah, Syed Tasadaque, additional, Guiry, Patrick J., additional, El-Osta, Assam, additional, Jandeleit-Dahm, Karin, additional, Cooper, Mark E., additional, Godson, Catherine, additional, and Kantharidis, Phillip, additional

Published
2018
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149. Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis

Author

Brennan, Eoin, primary, Wang, Bo, additional, McClelland, Aaron, additional, Mohan, Muthukumar, additional, Marai, Mariam, additional, Beuscart, Ophelie, additional, Derouiche, Sinda, additional, Gray, Stephen, additional, Pickering, Raelene, additional, Tikellis, Chris, additional, de Gaetano, Monica, additional, Barry, Mary, additional, Belton, Orina, additional, Ali-Shah, Syed Tasadaque, additional, Guiry, Patrick, additional, Jandeleit-Dahm, Karin A.M., additional, Cooper, Mark E., additional, Godson, Catherine, additional, and Kantharidis, Phillip, additional

Published
2017
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150. Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease

Author

Todd, Jennifer N, Dahlström, Emma H, Salem, Rany M, Sandholm, Niina, Forsblom, Carol, FinnDiane Study Group, McKnight, Amy J, Maxwell, Alexander P, Brennan, Eoin, Sadlier, Denise, Godson, Catherine, Groop, Per-Henrik, Hirschhorn, Joel N, and Florez, Jose C

Subjects
Adult, Male, Medical and Health Sciences, Body Mass Index, Kidney Failure, Cohort Studies, Endocrinology & Metabolism, FinnDiane Study Group, Risk Factors, Diabetes Mellitus, Prevalence, Humans, Albuminuria, Diabetic Nephropathies, Genetic Predisposition to Disease, Obesity, Longitudinal Studies, Chronic, Finland, Incidence, Middle Aged, Mendelian Randomization Analysis, Cross-Sectional Studies, Genetic Loci, Case-Control Studies, Female, Type 1
Abstract

Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% CI 1.03-1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% CI 0.93-0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% CI 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% CI 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur.

Published
2015

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