Defective activation of the MAPK/ERK pathway, leading to PARP1 and DNMT1 dysregulation, is a common defect in IgA nephropathy and Henoch-Schönlein purpura.

Journal of Nephrology
Annamaria MililloEugenio Sangiorgi

Abstract

Studies on IgA nephropathy (IgAN) have identified, through GWAS, linkage analysis, and pathway scanning, molecular defects in familial and sporadic IgAN patients. In our previous study, we identified a novel variant in the SPRY2 gene that segregates with the disease in one large family. The functional characterization of this variant led us to discover that the MAPK/ERK pathway was defective not only in this family, but also in two sporadic IgAN patients wild type for SPRY2. In the present study, we have deepened the molecular analysis of the MAPK/ERK pathway and extended our evaluation to a larger cohort of sporadic patients and to one additional family. We found that the ERK pathway is defective in IgAN patients and in patients affected by another IgA-mediated disorder, Henoch-Schönlein purpura (HSP). Furthermore, we found that two other proteins, PARP1 and DNMT1, respectively involved in DNA repair and in antibody class switching and methylation maintenance duties, were critically downregulated in IgAN and HSP patients. This study opens up the possibility that defective ERK activation, in some patients, leads to PARP1 and DNMT1 downregulation suggesting that IgAN could be the consequence of a dysregulated epigenetic maintena...Continue Reading

References

Sep 1, 1992·Clinical Immunology and Immunopathology·S M SmithH Tsukamoto
Apr 1, 1982·Transplantation·F SanfilippoR R Bollinger
Aug 3, 1999·The Journal of Experimental Medicine·C E SchraderJ Stavnezer
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Catherine A Hazzalin, Louis C Mahadevan
Sep 6, 2002·The New England Journal of Medicine·James V Donadio, Joseph P Grande
Jan 8, 2005·Oncogene·Anna RealePaola Caiafa
Apr 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Tiina M KauppinenRaymond A Swanson
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gabriela GorelikBruce Richardson
Mar 12, 2011·Clinical Journal of the American Society of Nephrology : CJASN·Jean-Claude Davin
Jul 26, 2011·Clinical & Developmental Immunology·Yusuke SuzukiYasuhiko Tomino
Aug 30, 2011·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Jürgen Floege
Sep 29, 2011·Journal of the American Society of Nephrology : JASN·Hitoshi SuzukiBruce A Julian
Mar 4, 2014·PloS One·Ali A AkhianiFredrik B Thorén
Mar 19, 2015·European Journal of Human Genetics : EJHG·Annamaria MililloEugenio Sangiorgi
Nov 19, 2015·Journal of Nephrology·Claudio Pozzi
Jan 9, 2016·Journal of Nephrology·Claudio PozziFrancesca Ferrario

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Citations

Dec 22, 2019·Journal of Nephrology·Bo-Yang XuHong Zhang
Mar 31, 2021·Immunology·Maria Manuela Rosado, Claudio Pioli
Jul 25, 2021·International Journal of Molecular Sciences·Hitomi SuginoMotonobu Nakamura

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