Cargando…

Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia

miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Lei, He, Sheng, Ling, Ling, Wang, Fangfang, Xu, Lei, Fang, Lei, Wu, Fan, Zhou, Shuting, Yang, Fan, Wei, Hongwei, Yu, Duonan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218191/
https://www.ncbi.nlm.nih.gov/pubmed/37239374
http://dx.doi.org/10.3390/genes14051011
_version_ 1785048715194531840
author Yang, Lei
He, Sheng
Ling, Ling
Wang, Fangfang
Xu, Lei
Fang, Lei
Wu, Fan
Zhou, Shuting
Yang, Fan
Wei, Hongwei
Yu, Duonan
author_facet Yang, Lei
He, Sheng
Ling, Ling
Wang, Fangfang
Xu, Lei
Fang, Lei
Wu, Fan
Zhou, Shuting
Yang, Fan
Wei, Hongwei
Yu, Duonan
author_sort Yang, Lei
collection PubMed
description miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.
format Online
Article
Text
id pubmed-10218191
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102181912023-05-27 Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia Yang, Lei He, Sheng Ling, Ling Wang, Fangfang Xu, Lei Fang, Lei Wu, Fan Zhou, Shuting Yang, Fan Wei, Hongwei Yu, Duonan Genes (Basel) Article miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors. MDPI 2023-04-29 /pmc/articles/PMC10218191/ /pubmed/37239374 http://dx.doi.org/10.3390/genes14051011 Text en © 2023 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
Yang, Lei
He, Sheng
Ling, Ling
Wang, Fangfang
Xu, Lei
Fang, Lei
Wu, Fan
Zhou, Shuting
Yang, Fan
Wei, Hongwei
Yu, Duonan
Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia
title Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia
title_full Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia
title_fullStr Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia
title_full_unstemmed Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia
title_short Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia
title_sort crosstalk between mir-144/451 and nrf2 during recovery from acute hemolytic anemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218191/
https://www.ncbi.nlm.nih.gov/pubmed/37239374
http://dx.doi.org/10.3390/genes14051011
work_keys_str_mv AT yanglei crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT hesheng crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT lingling crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT wangfangfang crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT xulei crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT fanglei crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT wufan crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT zhoushuting crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT yangfan crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT weihongwei crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia
AT yuduonan crosstalkbetweenmir144451andnrf2duringrecoveryfromacutehemolyticanemia