MiRNA-21-loaded chitosan nanoparticles ameliorate pancreatic apoptosis and oxidative stress in diabetic rats.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-02-14 DOI:10.1016/j.lfs.2025.123471

Eman H Thabet, Nehal A Khalil, Marwa M Essawy, Sahar A Harby, Amany A Solaiman, Hanaa M El Gazaerly, Yassmin H Khalifa

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引用次数: 0

Abstract

Background: Accelerated Pancreatic β-cell apoptosis and oxidative stress are the mainstays of type-1 diabetes. MicroRNA-21's (miRNA-21) role in regulating pancreatic β-cell function remains indefinable.

Material and methods: Five groups of rats were used in this study (healthy controls (Ia), controls that received only chitosan (CS) nanoparticles (NPs)(Ib), streptozotocin (STZ)-induced diabetics rats (II),STZ-induced diabetic rats that received only CS-NPs(III), and STZ-induced diabetic rats treated with mi-RNA-21-CS-NPs(IV). Sera were collected for measurement of fasting blood glucose levels (FBG), insulin, oxidative stress, and intraperitoneal glucose intolerance tests. Pancreatic tissue was collected after sacrifice partly for histological examination and for oxidative stress assessment and evaluation of PTEN/ AKT using qRT-PCR.

Key findings: We showed over-expression of cleaved-caspase-3 indicating accelerated apoptosis in the β-cell of STZ-induced diabetic rats. Apoptosis was significantly ameliorated by miRNA-21-CS. MiRNA-21-CS-NPs faithfully restored serum fasting insulin, and FBG, and reduced serum and pancreatic oxidative stress markers while enhancing the total antioxidant capacity. Histological examination revealed that miRNA-21 restored healthy β-cell architecture, decreased cleaved-caspase-3, and increased insulin secretion. Transmission electron microscopy revealed increased mitochondrial circularity that significantly correlated with an exaggerated oxidative stress profile as shown by high serum and pancreatic malondialdehyde (MDA), low glutathione peroxidase, and total antioxidant capacity in STZ-induced diabetes. This oxidative profile was reversed using miRNA-21-CS-NPs. Mi-RNA-21 therapy downregulated PTEN but increased AKT and pAKT expression. Altogether, we show that miRNA-21 restored normal islet β-cell structure and insulin secretion through PTEN inhibition.

Significance: miRNA-21- CS-NPs are promising targeted therapeutics that may effectively decrease the global burden of diabetes.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.