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Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

This study aimed to explore the spatio-temporal expression patterns of congenital anomalies of kidney and urinary tract (CAKUT) candidate genes, Fibroblast Growth Factor Receptor 1 (FGFR1), Fibroblast Growth Factor Receptor 2 (FGFR2) and Receptor-Interacting Protein Kinase 5 (RIP5), in human fetal k...

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Autores principales: Kelam, Nela, Racetin, Anita, Polović, Mirjana, Benzon, Benjamin, Ogorevc, Marin, Vukojević, Katarina, Glavina Durdov, Merica, Dunatov Huljev, Ana, Kuzmić Prusac, Ivana, Čarić, Davor, Raguž, Fila, Kostić, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779456/
https://www.ncbi.nlm.nih.gov/pubmed/36555181
http://dx.doi.org/10.3390/ijms232415537
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author Kelam, Nela
Racetin, Anita
Polović, Mirjana
Benzon, Benjamin
Ogorevc, Marin
Vukojević, Katarina
Glavina Durdov, Merica
Dunatov Huljev, Ana
Kuzmić Prusac, Ivana
Čarić, Davor
Raguž, Fila
Kostić, Sandra
author_facet Kelam, Nela
Racetin, Anita
Polović, Mirjana
Benzon, Benjamin
Ogorevc, Marin
Vukojević, Katarina
Glavina Durdov, Merica
Dunatov Huljev, Ana
Kuzmić Prusac, Ivana
Čarić, Davor
Raguž, Fila
Kostić, Sandra
author_sort Kelam, Nela
collection PubMed
description This study aimed to explore the spatio-temporal expression patterns of congenital anomalies of kidney and urinary tract (CAKUT) candidate genes, Fibroblast Growth Factor Receptor 1 (FGFR1), Fibroblast Growth Factor Receptor 2 (FGFR2) and Receptor-Interacting Protein Kinase 5 (RIP5), in human fetal kidney development (CTRL) and kidneys affected with CAKUT. Human fetal kidneys from the 22nd to 41st developmental week (duplex, hypoplastic, dysplastic, and controls) were stained with antibodies and analyzed by epifluorescence microscopy and RT−qPCR. The effect of CAKUT candidate genes on kidney nephrogenesis and function is confirmed by statistically significant variations in the spatio-temporal expression patterns of the investigated markers. The nuclear localization of FGFR1, elevated expression score of FGFR1 mRNA, the increased area percentage of FGFR1-positive cells in the kidney cortex, and the overall decrease in the expression after the peak at the 27th developmental week in dysplastic kidneys (DYS), suggest an altered expression pattern and protein function in response to CAKUT pathophysiology. The RT−qPCR analysis revealed a significantly higher FGFR2 mRNA expression score in the CAKUT kidneys compared to the CTRL. This increase could be due to the repair mechanism involving the downstream mediator, Extracellular Signal-Regulated Kinase 1/2 (ERK1/2). The expression of RIP5 during normal human kidney development was reduced temporarily, due to urine production and increased later since it undertakes additional functions in the maturation of the postnatal kidney and homeostasis, while the expression dynamics in CAKUT-affected kidneys exhibited a decrease in the percentage of RIP5-positive cells during the investigated developmental period. Our findings highlight the importance of FGFR1, FGFR2, and RIP5 as markers in normal and pathological kidney development.
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spelling pubmed-97794562022-12-23 Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Kelam, Nela Racetin, Anita Polović, Mirjana Benzon, Benjamin Ogorevc, Marin Vukojević, Katarina Glavina Durdov, Merica Dunatov Huljev, Ana Kuzmić Prusac, Ivana Čarić, Davor Raguž, Fila Kostić, Sandra Int J Mol Sci Article This study aimed to explore the spatio-temporal expression patterns of congenital anomalies of kidney and urinary tract (CAKUT) candidate genes, Fibroblast Growth Factor Receptor 1 (FGFR1), Fibroblast Growth Factor Receptor 2 (FGFR2) and Receptor-Interacting Protein Kinase 5 (RIP5), in human fetal kidney development (CTRL) and kidneys affected with CAKUT. Human fetal kidneys from the 22nd to 41st developmental week (duplex, hypoplastic, dysplastic, and controls) were stained with antibodies and analyzed by epifluorescence microscopy and RT−qPCR. The effect of CAKUT candidate genes on kidney nephrogenesis and function is confirmed by statistically significant variations in the spatio-temporal expression patterns of the investigated markers. The nuclear localization of FGFR1, elevated expression score of FGFR1 mRNA, the increased area percentage of FGFR1-positive cells in the kidney cortex, and the overall decrease in the expression after the peak at the 27th developmental week in dysplastic kidneys (DYS), suggest an altered expression pattern and protein function in response to CAKUT pathophysiology. The RT−qPCR analysis revealed a significantly higher FGFR2 mRNA expression score in the CAKUT kidneys compared to the CTRL. This increase could be due to the repair mechanism involving the downstream mediator, Extracellular Signal-Regulated Kinase 1/2 (ERK1/2). The expression of RIP5 during normal human kidney development was reduced temporarily, due to urine production and increased later since it undertakes additional functions in the maturation of the postnatal kidney and homeostasis, while the expression dynamics in CAKUT-affected kidneys exhibited a decrease in the percentage of RIP5-positive cells during the investigated developmental period. Our findings highlight the importance of FGFR1, FGFR2, and RIP5 as markers in normal and pathological kidney development. MDPI 2022-12-08 /pmc/articles/PMC9779456/ /pubmed/36555181 http://dx.doi.org/10.3390/ijms232415537 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kelam, Nela
Racetin, Anita
Polović, Mirjana
Benzon, Benjamin
Ogorevc, Marin
Vukojević, Katarina
Glavina Durdov, Merica
Dunatov Huljev, Ana
Kuzmić Prusac, Ivana
Čarić, Davor
Raguž, Fila
Kostić, Sandra
Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
title Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
title_full Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
title_fullStr Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
title_full_unstemmed Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
title_short Aberrations in FGFR1, FGFR2, and RIP5 Expression in Human Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
title_sort aberrations in fgfr1, fgfr2, and rip5 expression in human congenital anomalies of the kidney and urinary tract (cakut)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779456/
https://www.ncbi.nlm.nih.gov/pubmed/36555181
http://dx.doi.org/10.3390/ijms232415537
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