BM-MSCs alleviate diabetic nephropathy in male rats by regulating ER stress, oxidative stress, inflammation, and apoptotic pathways

Tarek Khamis; Adel Abdelkhalek; Hussein Abdellatif; Nourelden Dwidar; Ahmed Said; Rama Ahmed; Kerolos Wagdy; Rowina Elgarhy; Rawan Eltahan; Hisham Mohamed; Eman Said Amer; Maria Hanna; Tarek Ragab; Abdallah Kishk; Judy Wael; Eyad Sarhan; Linda Saweres; Mohamed Reda; Sara Elkomy; Abdalah Mohamed; Abdullah Samy; Ateya Khafaga; Youliana Shaker; Hamdy Yehia; Asma Alanazi; Mohammed Alassiri; Emil Tîrziu; Iulia Maria Bucur; Ahmed Hamed Arisha

doi:10.3389/fphar.2023.1265230

BM-MSCs alleviate diabetic nephropathy in male rats by regulating ER stress, oxidative stress, inflammation, and apoptotic pathways

Front Pharmacol. 2023 Nov 16:14:1265230. doi: 10.3389/fphar.2023.1265230. eCollection 2023.

Authors

Tarek Khamis¹, Adel Abdelkhalek², Hussein Abdellatif^{3

4}, Nourelden Dwidar², Ahmed Said², Rama Ahmed², Kerolos Wagdy², Rowina Elgarhy², Rawan Eltahan², Hisham Mohamed², Eman Said Amer², Maria Hanna², Tarek Ragab², Abdallah Kishk², Judy Wael², Eyad Sarhan², Linda Saweres², Mohamed Reda², Sara Elkomy², Abdalah Mohamed², Abdullah Samy², Ateya Khafaga², Youliana Shaker², Hamdy Yehia², Asma Alanazi^{5

6}, Mohammed Alassiri^{6

7

8}, Emil Tîrziu⁹, Iulia Maria Bucur⁹, Ahmed Hamed Arisha^{10

11}

Affiliations

¹ Department of Pharmacology and Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
² Faculty of Veterinary Medicine, Badr University in Cairo, Badr, Egypt.
³ Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
⁴ Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁵ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
⁶ King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
⁷ Department of Basic Sciences, College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
⁸ Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC), Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia.
⁹ Department of Animal Production and Veterinary Public Health, Faculty of Veterinary Medicine, University of Life Sciences, "King Mihai I" from Timisoara [ULST], Timisoara, Romania.
¹⁰ Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr, Egypt.
¹¹ Department of Physiology, Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

Abstract

Introduction: Diabetic nephropathy (DN), a chronic kidney disease, is a major cause of end-stage kidney disease worldwide. Mesenchymal stem cells (MSCs) have become a promising option to mitigate several diabetic complications. Methods: In this study, we evaluated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of STZ-induced DN. After the confirmation of diabetes, rats were treated with BM-MSCs and sacrificed at week 12 after treatment. Results: Our results showed that STZ-induced DN rats had extensive histopathological changes, significant upregulation in mRNA expression of renal apoptotic markers, ER stress markers, inflammatory markers, fibronectin, and intermediate filament proteins, and reduction of positive immunostaining of PCNA and elevated P53 in kidney tissue compared to the control group. BM-MSC therapy significantly improved renal histopathological changes, reduced renal apoptosis, ER stress, inflammation, and intermediate filament proteins, as well as increased positive immunostaining of PCNA and reduced P53 in renal tissue compared to the STZ-induced DN group. Conclusion: In conclusion, our study indicates that BM-MSCs may have therapeutic potential for the treatment of DN and provide important insights into their potential use as a novel therapeutic approach for DN.

Keywords: ER stress; apoptosis; bone marrow-derived mesenchymal stem cells; diabetes; diabetic nephropathy; inflammation; intermediate filament proteins; mesenchymal stem cells.

Copyright © 2023 Khamis, Abdelkhalek, Abdellatif, Dwidar, Said, Ahmed, Wagdy, Elgarhy, Eltahan, Mohamed, Said Amer, Hanna, Ragab, Kishk, Wael, Sarhan, Saweres, Reda, Elkomy, Mohamed, Samy, Khafaga, Shaker, Yehia, Alanazi, Alassiri, Tîrziu, Bucur and Arisha.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research received no external funding, and the APC was funded by the project 6PFE of the University of Life Sciences “King Mihai I” from Timisoara and the Research Institute for Biosecurity and Bioengineering from Timisoara, Romania.