Breast milk MSCs upregulated β-cells PDX1, Ngn3, and PCNA expression via remodeling ER stress /inflammatory /apoptotic signaling pathways in type 1 diabetic rats.

Autor: Khamis T; Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt; Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt. Electronic address: Khamistarek13@gmail.com., Abdelalim AF; Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt., Saeed AA; Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt., Edress NM; Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt., Nafea A; Department of Pediatrics, Faculty of Medicine, Zagazig University, 44519, Zagazig, Egypt., Ebian HF; Department of Clinical Pathology, Faculty of Medicine, Zagazig University, 44519, Zagazig, Egypt., Algendy R; Department of Milk Hygiene, Food Control Department, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt., Hendawy DM; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, 44511, Zagazig, Egypt., Arisha AH; Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Cairo, Egypt; Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt; Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt. Electronic address: vetahmedhamed@zu.edu.eg., Abdallah SH; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, 44511, Zagazig, Egypt.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2021 Aug 15; Vol. 905, pp. 174188. Date of Electronic Publication: 2021 May 15.
DOI: 10.1016/j.ejphar.2021.174188
Abstrakt: Type 1 diabetes mellitus (T1DM) is one of the autoimmune diseases characterized by beta-cell dysfunction with serious health complications. Br-MSCs represent a novel valid candidate in regenerative medicine disciplines. Yet, the full potential of Br-MSCs in managing type 1 diabetes remains elusive. Indeed, this study was designed to explore a novel approach investigating the possible regenerative capacity of Br-MSCs in type1 diabetic islet on the level of the cellular mRNA expression of different molecular pathways involved in pancreatic beta-cell dysfunction. Sixty adult male Sprague-Dawley rats were randomly assigned into 3 groups (20 rats each); the control group, type1 diabetic group, and the type 1 diabetic Br-MSCs treated group. And, for the first time, our results revealed that intraperitoneally transplanted Br-MSCs homed to the diabetic islet and improved fasting blood glucose, serum insulin level, pancreatic oxidative stress, upregulated pancreatic mRNA expression for: regenerative markers (Pdx1, Ngn3, PCNA), INS, beta-cell receptors (IRS1, IRβ, PPARγ), pancreatic growth factors (IGF-1, VEGFβ1, FGFβ), anti-inflammatory cytokine (IL10) and anti-apoptotic marker (BCL2) too, Br-MSCs downregulated pancreatic mRNA expression for: inflammatory markers (NFKβ, TNFα, IL1β, IL6, IL8, MCP1), apoptotic markers for both intrinsic and extrinsic pathways (FAS, FAS-L, P53, P38, BAX, Caspase3), ER stress markers (ATF6, ATF3, ATF4, BIP, CHOP, JNK, XBP1) and autophagy inhibitor (mTOR). In conclusion, Br-MSCs could be considered as a new insight in beta cell regenerative therapy improving the deteriorated diabetic islet microenvironment via modulating; ER stress, inflammatory, and apoptotic signaling pathways besides, switching on the cellular quality control system (autophagy) thus enhancing beta-cell function.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: