Breast milk MSCs upregulated β-cells PDX1, Ngn3, and PCNA expression via remodeling ER stress /inflammatory /apoptotic signaling pathways in type 1 diabetic rats.
Animals
Apoptosis
/ genetics
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Diabetes Mellitus, Experimental
/ metabolism
Diabetes Mellitus, Type 1
/ metabolism
Endoplasmic Reticulum Stress
/ genetics
Glycemic Control
Homeodomain Proteins
/ genetics
Inflammation
/ genetics
Insulin
/ genetics
Insulin-Secreting Cells
/ metabolism
Lipid Peroxidation
Male
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ metabolism
Milk, Human
/ chemistry
Nerve Tissue Proteins
/ genetics
Oxidative Stress
Proliferating Cell Nuclear Antigen
/ genetics
Rats, Sprague-Dawley
Receptor, Insulin
/ genetics
Signal Transduction
Trans-Activators
/ genetics
Up-Regulation
Apoptosis
Autophagy
Br-MSCs
Diabetes
ER stress
Oxidative stress
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
15 Aug 2021
15 Aug 2021
Historique:
received:
13
01
2021
revised:
30
04
2021
accepted:
12
05
2021
pubmed:
19
5
2021
medline:
12
8
2021
entrez:
18
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34004210
pii: S0014-2999(21)00341-1
doi: 10.1016/j.ejphar.2021.174188
pii:
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Homeodomain Proteins
0
Insulin
0
Nerve Tissue Proteins
0
Neurog3 protein, rat
0
Proliferating Cell Nuclear Antigen
0
Trans-Activators
0
pancreatic and duodenal homeobox 1 protein
0
Receptor, Insulin
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
174188Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.