Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations
Chronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to investigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes i...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/8/2149 |
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| author | Tarek Khamis Amira Ebrahim Alsemeh Asma Alanazi Asmaa Monir Eltaweel Heba M. Abdel-Ghany Doaa M. Hendawy Adel Abdelkhalek Mahmoud A. Said Heba H. Awad Basma Hamed Ibrahim Dina Mohamed Mekawy Corina Pascu Crista Florin Ahmed Hamed Arisha |
| author_facet | Tarek Khamis Amira Ebrahim Alsemeh Asma Alanazi Asmaa Monir Eltaweel Heba M. Abdel-Ghany Doaa M. Hendawy Adel Abdelkhalek Mahmoud A. Said Heba H. Awad Basma Hamed Ibrahim Dina Mohamed Mekawy Corina Pascu Crista Florin Ahmed Hamed Arisha |
| author_sort | Tarek Khamis |
| collection | DOAJ |
| description | Chronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to investigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes in CKD. Eighty adult male Sprague Dawley rats were randomly assigned to one of six groups, including control, nephropathy, nephropathy + conditioned media (CM), nephropathy + Br-MSCs, nephropathy + Br-MSCs derived exosomes (Br-MSCs-EXOs), and nephropathy + Br-MSCs + Br-MSCs-EXOs. Before administration, Br-MSCs and Br-MSCs-EXOs were isolated, identified, and labeled with PKH-26. SOX2, Nanog, and OCT3/4 expression levels in Br-MSCs and miR-29b, miR-181, and Let-7b in both Br-MSCs and Br-MSCs-EXOs were assayed. Twelve weeks after transplantation, renal function tests, oxidative stress, expression of the long non-coding RNA SNHG-7, autophagy, fibrosis, and expression of profibrotic miR-34a and antifibrotic miR-29b, miR-181, and Let-7b were measured in renal tissues. Immunohistochemical analysis for renal Beclin-1, LC3-II, and P62, Masson trichome staining, and histopathological examination of kidney tissues were also performed. The results showed that Br-MSCs expressed SOX2, Nanog, and OCT3/4, while both Br-MSCs and Br-MSCs-EXOs expressed antifibrotic miR-181, miR-29b, and Let-7b, with higher expression levels in exosomes than in Br-MSCs. Interestingly, the administration of Br-MSCs + EXOs, EXOs, and Br-MSCs improved renal function tests, reduced renal oxidative stress, upregulated the renal expression of SNHG-7, AMPK, ULK-1, Beclin-1, LC3, miR-29b, miR-181, Let-7b, and Smad-7, downregulated the renal expression of miR-34a, AKT, mTOR, P62, TGF-β, Smad-3, and Coli-1, and ameliorated renal pathology. Thus, Br-MSCs and/or their derived exosomes appear to reduce adenine-induced renal damage by secreting antifibrotic microRNAs and potentiate renal autophagy by modulating SNHG-7 expression. |
| first_indexed | 2024-03-10T23:39:37Z |
| format | Article |
| id | doaj.art-797eb16682044e89ac9c252ede361baa |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:37Z |
| publishDate | 2023-08-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-797eb16682044e89ac9c252ede361baa2023-11-19T02:37:37ZengMDPI AGPharmaceutics1999-49232023-08-01158214910.3390/pharmaceutics15082149Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic RegulationsTarek Khamis0Amira Ebrahim Alsemeh1Asma Alanazi2Asmaa Monir Eltaweel3Heba M. Abdel-Ghany4Doaa M. Hendawy5Adel Abdelkhalek6Mahmoud A. Said7Heba H. Awad8Basma Hamed Ibrahim9Dina Mohamed Mekawy10Corina Pascu11Crista Florin12Ahmed Hamed Arisha13Department of Pharmacology and Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, EgyptHuman Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptCollege of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh 11481, Saudi ArabiaHuman Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptDepartment of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, EgyptBiochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptDepartment of Food Hygiene, Safety and Technology, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, EgyptZagazig University Hospital, Zagazig University, Zagazig 44511, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza 12451, EgyptPathology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptMedical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11562, EgyptFaculty of Veterinary Medicine, University of Life Sciences, King Mihai I from Timisoara [ULST], Aradului St. 119, 300645 Timisoara, RomaniaDepartment of Soil Science, Faculty of Agriculture, University of Life Sciences, King Mihai I from Timisoara [ULST], Aradului St. 119, 300645 Timisoara, RomaniaDepartment of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, EgyptChronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to investigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes in CKD. Eighty adult male Sprague Dawley rats were randomly assigned to one of six groups, including control, nephropathy, nephropathy + conditioned media (CM), nephropathy + Br-MSCs, nephropathy + Br-MSCs derived exosomes (Br-MSCs-EXOs), and nephropathy + Br-MSCs + Br-MSCs-EXOs. Before administration, Br-MSCs and Br-MSCs-EXOs were isolated, identified, and labeled with PKH-26. SOX2, Nanog, and OCT3/4 expression levels in Br-MSCs and miR-29b, miR-181, and Let-7b in both Br-MSCs and Br-MSCs-EXOs were assayed. Twelve weeks after transplantation, renal function tests, oxidative stress, expression of the long non-coding RNA SNHG-7, autophagy, fibrosis, and expression of profibrotic miR-34a and antifibrotic miR-29b, miR-181, and Let-7b were measured in renal tissues. Immunohistochemical analysis for renal Beclin-1, LC3-II, and P62, Masson trichome staining, and histopathological examination of kidney tissues were also performed. The results showed that Br-MSCs expressed SOX2, Nanog, and OCT3/4, while both Br-MSCs and Br-MSCs-EXOs expressed antifibrotic miR-181, miR-29b, and Let-7b, with higher expression levels in exosomes than in Br-MSCs. Interestingly, the administration of Br-MSCs + EXOs, EXOs, and Br-MSCs improved renal function tests, reduced renal oxidative stress, upregulated the renal expression of SNHG-7, AMPK, ULK-1, Beclin-1, LC3, miR-29b, miR-181, Let-7b, and Smad-7, downregulated the renal expression of miR-34a, AKT, mTOR, P62, TGF-β, Smad-3, and Coli-1, and ameliorated renal pathology. Thus, Br-MSCs and/or their derived exosomes appear to reduce adenine-induced renal damage by secreting antifibrotic microRNAs and potentiate renal autophagy by modulating SNHG-7 expression.https://www.mdpi.com/1999-4923/15/8/2149mesenchymal stem cellsexosomesmiRNAmRNAlong-non-coding RNA |
| spellingShingle | Tarek Khamis Amira Ebrahim Alsemeh Asma Alanazi Asmaa Monir Eltaweel Heba M. Abdel-Ghany Doaa M. Hendawy Adel Abdelkhalek Mahmoud A. Said Heba H. Awad Basma Hamed Ibrahim Dina Mohamed Mekawy Corina Pascu Crista Florin Ahmed Hamed Arisha Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations Pharmaceutics mesenchymal stem cells exosomes miRNA mRNA long-non-coding RNA |
| title | Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations |
| title_full | Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations |
| title_fullStr | Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations |
| title_full_unstemmed | Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations |
| title_short | Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations |
| title_sort | breast milk mesenchymal stem cells and or derived exosomes mitigated adenine induced nephropathy via modulating renal autophagy and fibrotic signaling pathways and their epigenetic regulations |
| topic | mesenchymal stem cells exosomes miRNA mRNA long-non-coding RNA |
| url | https://www.mdpi.com/1999-4923/15/8/2149 |
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