The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1

The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic effica...

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Main Authors: Hyun Seop Cho, Ha Nee Jang, Myeong Hee Jung, Si Jung Jang, Sang-Ho Jeong, Tae Won Lee, Eunjin Bae, Se-Ho Chang, Dong Jun Park, Jin Hyun Kim
Format: Article
Language:English
Published: SAGE Publishing 2020-06-01
Series:European Journal of Inflammation
Online Access:https://doi.org/10.1177/2058739220934563
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author Hyun Seop Cho
Ha Nee Jang
Myeong Hee Jung
Si Jung Jang
Sang-Ho Jeong
Tae Won Lee
Eunjin Bae
Se-Ho Chang
Dong Jun Park
Jin Hyun Kim
author_facet Hyun Seop Cho
Ha Nee Jang
Myeong Hee Jung
Si Jung Jang
Sang-Ho Jeong
Tae Won Lee
Eunjin Bae
Se-Ho Chang
Dong Jun Park
Jin Hyun Kim
author_sort Hyun Seop Cho
collection DOAJ
description The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague–Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI.
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spelling doaj.art-968ec68d0402484ba8fdc15154da74a72022-12-22T01:26:22ZengSAGE PublishingEuropean Journal of Inflammation2058-73922020-06-011810.1177/2058739220934563The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1Hyun Seop Cho0Ha Nee Jang1Myeong Hee Jung2Si Jung Jang3Sang-Ho Jeong4Tae Won Lee5Eunjin Bae6Se-Ho Chang7Dong Jun Park8Jin Hyun Kim9Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of KoreaDepartment of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of KoreaBiomedical Research Institute, Gyeongsang National University Hospital, Jinju, Republic of KoreaBiomedical Research Institute, Gyeongsang National University Hospital, Jinju, Republic of KoreaDepartment of General Surgery, Gyeongsang National University College of Medicine, Jinju, Republic of KoreaDepartment of General Surgery, Gyeongsang National University College of Medicine, Jinju, Republic of KoreaDepartment of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Republic of KoreaDepartment of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of KoreaInstitute of Health Science, Gyeongsang National University College of Medicine, Jinju, Republic of KoreaDepartment of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of KoreaThe therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague–Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI.https://doi.org/10.1177/2058739220934563
spellingShingle Hyun Seop Cho
Ha Nee Jang
Myeong Hee Jung
Si Jung Jang
Sang-Ho Jeong
Tae Won Lee
Eunjin Bae
Se-Ho Chang
Dong Jun Park
Jin Hyun Kim
The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1
European Journal of Inflammation
title The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1
title_full The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1
title_fullStr The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1
title_full_unstemmed The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1
title_short The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1
title_sort protective effect of human adiposederived mesenchymal stem cells on cisplatin induced nephrotoxicity is dependent on their level of expression of heme oxygenase 1
url https://doi.org/10.1177/2058739220934563
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