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Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis
BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324505/ https://www.ncbi.nlm.nih.gov/pubmed/37424951 http://dx.doi.org/10.4252/wjsc.v15.i6.617 |
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author | Hu, Qiong-Dan Tan, Rui-Zhi Zou, Yuan-Xia Li, Jian-Chun Fan, Jun-Ming Kantawong, Fahsai Wang, Li |
author_facet | Hu, Qiong-Dan Tan, Rui-Zhi Zou, Yuan-Xia Li, Jian-Chun Fan, Jun-Ming Kantawong, Fahsai Wang, Li |
author_sort | Hu, Qiong-Dan |
collection | PubMed |
description | BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion. However, the protective effect and underlying mechanism of CA-pretreated MSCs (MSCs(CA)) on podocytes in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) mice remain unclear. AIM: To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved. METHODS: ADR was used to induce FSGS in mice, and MSCs, CA, or MSCs(CA) were administered to mice. Their protective effect and possible mechanism of action on podocytes were observed by Western blot, immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction. In vitro, ADR was used to stimulate mouse podocytes (MPC5) to induce injury, and the supernatants from MSC-, CA-, or MSCs(CA)-treated cells were collected to observe their protective effects on podocytes. Subsequently, the apoptosis of podocytes was detected in vivo and in vitro by Western blot, TUNEL assay, and immunofluorescence. Overexpression of Smad3, which is involved in apoptosis, was then induced to evaluate whether the MSCs(CA)-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells. RESULTS: CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells. Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells, which was reversed by MSC(CA) treatment more significantly than by MSCs or CA alone. When Smad3 was overexpressed in MPC5 cells, MSCs(CA) could not fulfill their potential to inhibit podocyte apoptosis. CONCLUSION: MSCs(CA) enhance the protection of MSCs against ADR-induced podocyte apoptosis. The underlying mechanism may be related to MSCs(CA)-targeted inhibition of p-Smad3 in podocytes. |
format | Online Article Text |
id | pubmed-10324505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-103245052023-07-07 Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis Hu, Qiong-Dan Tan, Rui-Zhi Zou, Yuan-Xia Li, Jian-Chun Fan, Jun-Ming Kantawong, Fahsai Wang, Li World J Stem Cells Basic Study BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion. However, the protective effect and underlying mechanism of CA-pretreated MSCs (MSCs(CA)) on podocytes in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) mice remain unclear. AIM: To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved. METHODS: ADR was used to induce FSGS in mice, and MSCs, CA, or MSCs(CA) were administered to mice. Their protective effect and possible mechanism of action on podocytes were observed by Western blot, immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction. In vitro, ADR was used to stimulate mouse podocytes (MPC5) to induce injury, and the supernatants from MSC-, CA-, or MSCs(CA)-treated cells were collected to observe their protective effects on podocytes. Subsequently, the apoptosis of podocytes was detected in vivo and in vitro by Western blot, TUNEL assay, and immunofluorescence. Overexpression of Smad3, which is involved in apoptosis, was then induced to evaluate whether the MSCs(CA)-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells. RESULTS: CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells. Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells, which was reversed by MSC(CA) treatment more significantly than by MSCs or CA alone. When Smad3 was overexpressed in MPC5 cells, MSCs(CA) could not fulfill their potential to inhibit podocyte apoptosis. CONCLUSION: MSCs(CA) enhance the protection of MSCs against ADR-induced podocyte apoptosis. The underlying mechanism may be related to MSCs(CA)-targeted inhibition of p-Smad3 in podocytes. Baishideng Publishing Group Inc 2023-06-26 2023-06-26 /pmc/articles/PMC10324505/ /pubmed/37424951 http://dx.doi.org/10.4252/wjsc.v15.i6.617 Text en ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Hu, Qiong-Dan Tan, Rui-Zhi Zou, Yuan-Xia Li, Jian-Chun Fan, Jun-Ming Kantawong, Fahsai Wang, Li Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
title | Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
title_full | Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
title_fullStr | Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
title_full_unstemmed | Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
title_short | Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
title_sort | synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324505/ https://www.ncbi.nlm.nih.gov/pubmed/37424951 http://dx.doi.org/10.4252/wjsc.v15.i6.617 |
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