Cargando…

Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells

Aging is one of the causative agents associated with heart failure. Cell-based therapies show potential in the treatment of cardiac aging due to the characteristics of stem cells, including differentiation and the paracrine effect. This study aimed to investigate in detail the mechanism related to b...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Wei-Syun, Liao, Wei-Yu, Chang, Chin-Hsien, Chen, Tung-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369306/
https://www.ncbi.nlm.nih.gov/pubmed/35956039
http://dx.doi.org/10.3390/jcm11154419
_version_ 1784766411779866624
author Hu, Wei-Syun
Liao, Wei-Yu
Chang, Chin-Hsien
Chen, Tung-Sheng
author_facet Hu, Wei-Syun
Liao, Wei-Yu
Chang, Chin-Hsien
Chen, Tung-Sheng
author_sort Hu, Wei-Syun
collection PubMed
description Aging is one of the causative agents associated with heart failure. Cell-based therapies show potential in the treatment of cardiac aging due to the characteristics of stem cells, including differentiation and the paracrine effect. This study aimed to investigate in detail the mechanism related to biomolecules released from mesenchymal stem cells in the treatment of cardiac aging. In vitro and in vivo models were designed to explore the above hypothesis. Experimental results from the in vitro model indicated that the elevation of oxidative stress, the expression of aging marker p53, and the suppression of antioxidant marker SOD2 could be found in D-galactose-stressed H9c2 cardiomyoblasts. The co-culture of D-galactose-stressed H9c2 with mesenchymal stem cells significantly improved the above pathological signaling. An animal model revealed that the change in cardiac structure, the accumulation of fibrotic collagen, and the activation of the above pathological signaling could be observed in heart tissues of D-galactose-stressed rats. After the rats had received mesenchymal stem cells, all the pathological conditions were significantly improved in D-galactose-stressed hearts. Further evidence indicated that the release of the survival marker IGF-1 was detected in a stem-cell-conditioned medium. Significant increases in cell viability and the expression of SOD2, as well as a reduction in oxidative stress and the suppression of p53, were found in D-galactose-stressed H9c2 cells cultured with a stem-cell-conditioned medium, whereas the depletion of IGF-1 in stem-cell-conditioned medium diminished the antiaging effect on H9c2 cells. In conclusion, the paracrine release of IGF-1 from mesenchymal stem cells increases the expression of antioxidant marker SOD2, and the expression of SOD2 reduces oxidative stress as well as suppresses p53, leading to a reduction in cardiac senescence in D-galactose-stressed rats.
format Online
Article
Text
id pubmed-9369306
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93693062022-08-12 Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells Hu, Wei-Syun Liao, Wei-Yu Chang, Chin-Hsien Chen, Tung-Sheng J Clin Med Article Aging is one of the causative agents associated with heart failure. Cell-based therapies show potential in the treatment of cardiac aging due to the characteristics of stem cells, including differentiation and the paracrine effect. This study aimed to investigate in detail the mechanism related to biomolecules released from mesenchymal stem cells in the treatment of cardiac aging. In vitro and in vivo models were designed to explore the above hypothesis. Experimental results from the in vitro model indicated that the elevation of oxidative stress, the expression of aging marker p53, and the suppression of antioxidant marker SOD2 could be found in D-galactose-stressed H9c2 cardiomyoblasts. The co-culture of D-galactose-stressed H9c2 with mesenchymal stem cells significantly improved the above pathological signaling. An animal model revealed that the change in cardiac structure, the accumulation of fibrotic collagen, and the activation of the above pathological signaling could be observed in heart tissues of D-galactose-stressed rats. After the rats had received mesenchymal stem cells, all the pathological conditions were significantly improved in D-galactose-stressed hearts. Further evidence indicated that the release of the survival marker IGF-1 was detected in a stem-cell-conditioned medium. Significant increases in cell viability and the expression of SOD2, as well as a reduction in oxidative stress and the suppression of p53, were found in D-galactose-stressed H9c2 cells cultured with a stem-cell-conditioned medium, whereas the depletion of IGF-1 in stem-cell-conditioned medium diminished the antiaging effect on H9c2 cells. In conclusion, the paracrine release of IGF-1 from mesenchymal stem cells increases the expression of antioxidant marker SOD2, and the expression of SOD2 reduces oxidative stress as well as suppresses p53, leading to a reduction in cardiac senescence in D-galactose-stressed rats. MDPI 2022-07-29 /pmc/articles/PMC9369306/ /pubmed/35956039 http://dx.doi.org/10.3390/jcm11154419 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
Hu, Wei-Syun
Liao, Wei-Yu
Chang, Chin-Hsien
Chen, Tung-Sheng
Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
title Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
title_full Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
title_fullStr Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
title_full_unstemmed Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
title_short Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
title_sort paracrine igf-1 activates sod2 expression and regulates ros/p53 axis in the treatment of cardiac damage in d-galactose-induced aging rats after receiving mesenchymal stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369306/
https://www.ncbi.nlm.nih.gov/pubmed/35956039
http://dx.doi.org/10.3390/jcm11154419
work_keys_str_mv AT huweisyun paracrineigf1activatessod2expressionandregulatesrosp53axisinthetreatmentofcardiacdamageindgalactoseinducedagingratsafterreceivingmesenchymalstemcells
AT liaoweiyu paracrineigf1activatessod2expressionandregulatesrosp53axisinthetreatmentofcardiacdamageindgalactoseinducedagingratsafterreceivingmesenchymalstemcells
AT changchinhsien paracrineigf1activatessod2expressionandregulatesrosp53axisinthetreatmentofcardiacdamageindgalactoseinducedagingratsafterreceivingmesenchymalstemcells
AT chentungsheng paracrineigf1activatessod2expressionandregulatesrosp53axisinthetreatmentofcardiacdamageindgalactoseinducedagingratsafterreceivingmesenchymalstemcells