In-Hwan Song1, Kyong-Jin Jung1, Tae-Jin Lee1, Joo-Young Kim1, Eon-Gi Sung1, Young Chul Bae2, Yong Hoon Park3. 1. Department of Anatomy, Yeungnam University College of Medicine, Daegu, South Korea. 2. Pediatrics, Yeungnam University College of Medicine, Daegu, South Korea. 3. Department of Anatomy, Kyungpook National University School of Dentistry, Daegu, South Korea.
Abstract
AIM: This study aimed to evaluate the molecular mechanism mitigating progress of chronic nephropathy by mesenchymal stem cells (MSCs). METHODS: Rats were divided into normal control (Normal), adriamycin (ADR)+vehicle (CON), and ADR+MSC (MSC) groups. Nephropathy was induced by ADR (4 mg/kg) and MSCs (2 × 106 ) were injected. Rats were euthanized 1 or 6 weeks after ADR injection. NF-kB, MAPKs, inflammation, oxidative stress, profibrotic molecules, and nephrin expression were evaluated. Electron and light microscopy were used for structural analysis. MSCs were co-cultured with renal tubular epithelial cells or splenocytes to evaluate relation with oxidative stress and inflammatory molecules RESULTS: Adriamycin treatment upregulated inflammation, oxidative stress, and profibrotic molecules; this was mitigated by MSCs. Glomerulosclerosis and interstitial fibrosis were observed in ADR-treated groups, and were more prominent in the CON group than in the MSC group. Fusion of foot processes and loss of slit diaphragms were also more prominent in the CON group than in the MSC group. In vitro, MSCs reduced oxidative stress related molecules, inflammatory cytokines, and NF-kB transcription. MSC- or ADR-induced regulation of NF-kB transcriptional activity was confirmed by a luciferase reporter assay. CONCLUSIONS: Mesenchymal stem cells attenuate ADR-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of NF-kB.
AIM: This study aimed to evaluate the molecular mechanism mitigating progress of chronic nephropathy by mesenchymal stem cells (MSCs). METHODS:Rats were divided into normal control (Normal), adriamycin (ADR)+vehicle (CON), and ADR+MSC (MSC) groups. Nephropathy was induced by ADR (4 mg/kg) and MSCs (2 × 106 ) were injected. Rats were euthanized 1 or 6 weeks after ADR injection. NF-kB, MAPKs, inflammation, oxidative stress, profibrotic molecules, and nephrin expression were evaluated. Electron and light microscopy were used for structural analysis. MSCs were co-cultured with renal tubular epithelial cells or splenocytes to evaluate relation with oxidative stress and inflammatory molecules RESULTS:Adriamycin treatment upregulated inflammation, oxidative stress, and profibrotic molecules; this was mitigated by MSCs. Glomerulosclerosis and interstitial fibrosis were observed in ADR-treated groups, and were more prominent in the CON group than in the MSC group. Fusion of foot processes and loss of slit diaphragms were also more prominent in the CON group than in the MSC group. In vitro, MSCs reduced oxidative stress related molecules, inflammatory cytokines, and NF-kB transcription. MSC- or ADR-induced regulation of NF-kB transcriptional activity was confirmed by a luciferase reporter assay. CONCLUSIONS: Mesenchymal stem cells attenuate ADR-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of NF-kB.
Authors: María José Ramírez-Bajo; Javier Martín-Ramírez; Stefania Bruno; Chiara Pasquino; Elisenda Banon-Maneus; Jordi Rovira; Daniel Moya-Rull; Marta Lazo-Rodriguez; Josep M Campistol; Giovanni Camussi; Fritz Diekmann Journal: Front Cell Dev Biol Date: 2020-05-05
Authors: Amira Awadalla; Abdelaziz M Hussein; Yousra M El-Far; Fardous F El-Senduny; Nashwa Barakat; Eman T Hamam; Hanaa M Abdeen; Mohamed El-Sherbiny; Mohamed S Serria; Amira A Sarhan; Asmaa M Sena; Ahmed A Shokeir Journal: Biomedicines Date: 2022-05-31