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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis
Qiong-Dan Hu, Rui-Zhi Tan, Yuan-Xia Zou, Jian-Chun Li, Jun-Ming Fan, Fahsai Kantawong, Li Wang
Qiong-Dan Hu, Rui-Zhi Tan, Fahsai Kantawong, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
Qiong-Dan Hu, Rui-Zhi Tan, Yuan-Xia Zou, Jian-Chun Li, Li Wang, Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
Qiong-Dan Hu, Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
Yuan-Xia Zou, Jian-Chun Li, Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
Jun-Ming Fan, Department of Nephrology, The Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Author contributions: Wang L and Fahsai K contributed equally to this article as co-corresponding authors; Wang L and Fahsai K designed the study and supervised the laboratory experiments; Hu QD conducted the experiments and drafted the manuscript; Tan RZ assisted with the experiments; Zou YX and Li JC collected the samples; Fan JM and Wang L contributed new reagents and analytic tools; and all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China (General Program), No. 82205002; Science and Technology Project of Sichuan Province, No. 2022YFS0621, No. 21ZDYF0348, and No. 2022NSFSC1459; Luzhou-Southwest Medical University Science and Technology Strategic Cooperation Project, No. 2021LZXNYD-P04; and Southwest Medical University of Affiliated Traditional Medicine Hospital Project, No. 2022-CXTD-03.
Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Animal Ethics Committee of Southwest Medical University (Approval No. 20221031-012).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: All data are available from the corresponding author upon reasonable request Wangli120@swmu.edu.cn.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: 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. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Li Wang, PhD, Professor, Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182 Chunhui Road, Longmatan District, Luzhou 646000, Sichuan Province, China. wangli120@swmu.edu.cn
Received: March 29, 2023
Peer-review started: March 29, 2023
First decision: April 25, 2023
Revised: April 28, 2023
Accepted: May 25, 2023
Article in press: May 25, 2023
Published online: June 26, 2023
ARTICLE HIGHLIGHTS
Research background
Focal segmental glomerulosclerosis (FSGS) has become a global public health problem due to its high incidence and lack of treatment. Prevention of podocyte apoptosis is essential in the treatment of FSGS. Bone marrow-derived mesenchymal stem cells (BMSCs) have been found to protect podocytes, but have some limitations, such as low survival rate in vivo and poor homing function. In our previous study, calycosin (CA)-pretreated BMSCs enhanced the antifibrotic activity in kidneys compared with BMSCs. Therefore, CA-pretreated MSCs are expected to be a new method to protect podocytes in the treatment of FSGS.
Research motivation
Although MSCs have been confirmed to improve podocyte apoptosis in mice, their availability and effectiveness in vivo are limited. Currently, there is still a lack of effective therapeutic methods for FSGS, and their mechanism of action is not clear.
Research objectives
To evaluate the therapeutic effect of CA-pretreated BMSCs in a mouse model of adriamycin (ADR)-induced FSGS in vivo and MPC5 cells in vivo.
Research methods
MSCsCA were compared with MSCs or CA to observe their inhibitory effects on podocyte apoptosis in mice with ADR-induced FSGS in vivo and ADR-treated MPC5 cells in vitro, to explore the possible mechanism by which MSCsCA improves podocyte apoptosis.
Research results
In vivo results showed that MSCsCA reduced podocyte apoptosis, improved podocyte injury and depletion, alleviated glomerulosclerosis and albuminuria, and downregulated p-Smad3 expression in ADR-induced FSGS mice, which were superior to MSCs and CA. Similar to in vivo studies, MSCsCA alleviated ADR-induced apoptosis of MPC5 cells more significantly than MSCs and CA. Through rescue experiments, we found that the potential of MSCsCA to protect podocytes may be realized through targeted inhibition of p-Smad3 expression.
Research conclusions
MSCsCA improve ADR-induced podocyte apoptosis by targeting Smad3 inhibition, which are superior to MSCs or CA.
Research perspectives
Our findings provide a new potential strategy for the treatment of FSGS.
