Effect of combined therapy of mesenchymal stem cells with GLP-1 receptor agonist, exenatide, on early-onset nephropathy induced in diabetic rats

Copyright © 2020 Elsevier B.V. All rights reserved..

Diabetic nephropathy is the principal cause of end-stage renal failure and current interventions for its recession remains unsatisfactory. Mesenchymal stem cells (MSCs) hold an attractive source for renovating injured tissues. Unfortunately, limited self-renewal and migration capacity of MSCs after transplantation hinder their clinical applicability which demands a new policy for enhancing their biological functions. This study aimed to investigate whether the renoprotective potential of adipose-derived MSCs (ADMSCs) in diabetic rats could be promoted by exenatide, a glucagon-like peptide-1 (GLP-1) analogue. These effects were studied in type 2 diabetes mellitus rats which were administrated ADMSCs, exenatide or their combination four weeks post-induction. Four weeks later, renal function parameters were evaluated. To address the possible underlying mechanisms, parameters indicating glycolipid metabolism tolerance and oxidative stress biomarkers were assessed in renal tissues alongside evaluation of protein expression of tumor necrosis factor-alpha, transforming growth factor-beta1 and cleaved caspase-3. The results showed that the combined therapy had superior renoprotective effect as evident by significant improvement in kidney function and renal architecture changes through rebalancing of inflammatory, fibrotic and apoptotic markers. Based on these outcomes, ADMSCs with exenatide were supposed to effectively ameliorate diabetic renal dysfunction compared to ADMSCs solely, presenting a promise therapy for diabetic nephropathy with further clinical studies warranted to validate this effect.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:892

Enthalten in:

European journal of pharmacology - 892(2021) vom: 05. Feb., Seite 173721

Sprache:

Englisch

Beteiligte Personen:

Habib, Heba A [VerfasserIn]
Heeba, Gehan H [VerfasserIn]
Khalifa, Mohamed M A [VerfasserIn]

Links:

Volltext

Themen:

5W494URQ81
9P1872D4OL
Adipose-derived mesenchymal stem cell
Blood Glucose
Casp3 protein, rat
Caspase 3
Diabetic nephropathy
EC 3.4.22.-
Exenatide
Glp1r protein, rat
Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents
Journal Article
Streptozocin
Tgfb1 protein, rat
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 18.05.2021

Date Revised 26.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ejphar.2020.173721

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317277219