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miR-188-3p abolishes germacrone-mediated podocyte protection in a mouse model of diabetic nephropathy in type I diabetes through triggering mitochondrial injury
- Source :
- Bioengineered, Vol 13, Iss 1, Pp 774-788 (2022), Bioengineered, article-version (VoR) Version of Record
- Publication Year :
- 2022
- Publisher :
- Taylor & Francis Group, 2022.
-
Abstract
- Mitochondrial injury-triggered podocyte apoptosis is a major risk factor for diabetic nephropathy (DN). However, the detailed relationship between mitochondrial homeostasis and podocyte apoptosis remains unclear. The present study aimed to explore the role and functional mechanism of germacrone in DN in type I diabetes (type I DN). A mouse model of type I DN was established by injecting streptozocin, and a podocyte injury model was constructed using high glucose (HG) induction. Histopathology was detected by hematoxylin and eosin and periodic acid-Schiff staining. Transmission electron microscopy and flow cytometry were used to evaluate the mitochondrial function. Germacrone simultaneously reduced blood glucose, 24 h proteinuria, and other nephrotic symptoms in a type 1 DN mouse model. Moreover, germacrone protected against mitochondrial damage, limited reactive oxygen species (ROS) accumulation, and restored glutathione peroxidase (GPX) activity and GPX4 protein expression, subsequently preventing podocyte apoptosis. Mechanistically, the increased miR-188-3p expression in type I DN mice was reversed in germacrone-challenged DN mice. HG induced miR-188-3p expression and the miR-188-3p antagonist abolished the HG-mediated increase in ROS. Notably, miR-188-3p was found to have a therapeutic effect against DN by aggravating mitochondrial damage and podocyte apoptosis. Germacrone alleviates DN progression in type I diabetes by limiting podocyte apoptosis, which was partly counteracted by miR-188-3p upregulation. The combination of germacrone and miR-188-3p antagonists is expected to be an effective therapeutic strategy for DN. Abbreviations DN: diabetic nephropathy; Type I DN: DN in Type I diabetes; STZ: streptozocin; ROS: reactive oxygen species; NcRNAs: non-coding RNAs; UTR: untranslated regions; NC: negative control; BUN: blood urea nitrogen; BUA: blood uric acid; Ucr: urine creatinine; Scr: serum creatinine; PAS: Periodic Acid-Schiff; IF: Immunofluorescence; FISH: Fluorescence in situ hybridization; TUG1: taurine upregulated gene 1; GPX: Glutathione Peroxidase; GPX4: glutathione peroxidase 4; EMT: epithelial-mesenchymal transition
- Subjects :
- Male
podocyte
mir-188-3p
mitochondrial damage
Bioengineering
Germacrone
GPX4
Applied Microbiology and Biotechnology
Diabetes Mellitus, Experimental
Flow cytometry
Podocyte
Diabetic nephropathy
Mice
chemistry.chemical_compound
Downregulation and upregulation
medicine
Animals
Diabetic Nephropathies
chemistry.chemical_classification
Reactive oxygen species
medicine.diagnostic_test
Podocytes
Glutathione peroxidase
diabetic nephropathy
General Medicine
medicine.disease
Mitochondria
MicroRNAs
Diabetes Mellitus, Type 1
medicine.anatomical_structure
chemistry
Cancer research
germacrone
TP248.13-248.65
Research Article
Research Paper
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 21655987 and 21655979
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Bioengineered
- Accession number :
- edsair.doi.dedup.....4c2455ea3e47e36e730903c647e5d4a7