ArticleMolecular medicine (Cambridge, Mass.)2021
MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes.
Article in Molecular medicine (Cambridge, Mass.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Endothelial PDGF Signaling Dysregulation Impairs Testicular Interstitial Homeostasis in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Impact of Type 1 Diabetes on Testicular Microtubule Dynamics, Sperm Physiology, and Male Reproductive Health in Rat.International journal of molecular sciences · 2025Article
- Research progress of non-coding RNA regulating the role of PANoptosis in diabetes mellitus and its complications.Apoptosis : an international journal on programmed cell death · 2025Review
- FREQUENCY AND CORRELATES OF HYPOGONADISM AMONG A COHORT OF NIGERIAN MEN WITH TYPE 2 DIABETES MELLITUS.Annals of Ibadan postgraduate medicine · 2025Article
- The microRNA-mediated apoptotic signaling axis in male reproduction: a possible and targetable culprit in male infertility.Cell biology and toxicology · 2025Review
- Influence of aging and maternal protein restriction on PIWI-interacting RNA expression in the offspring rat ventral prostate.Scientific reports · 2024Article
- Protective Effect of Black Rice Cyanidin-3-Glucoside on Testicular Damage in STZ-Induced Type 1 Diabetic Rats.Foods (Basel, Switzerland) · 2024Article
- ERK5 Cooperates With MEF2C to Regulate Nr4a1 Transcription in MA-10 and MLTC-1 Leydig Cells.Endocrinology · 2023Article
- Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes.The Journal of pharmacology and experimental therapeutics · 2023Article
- Erectile Dysfunction Severity: The Role of Glycometabolic Compensation and Antihyperglycemic Drugs.Journal of clinical medicine · 2022Article
- Circ0007042 alleviates intervertebral disc degeneration by adsorbing miR-369 to upregulate BMP2 and activate the PI3K/AKt pathway.Arthritis research & therapy · 2022Article
- MicroRNA Profile of MA-104 Cell Line Associated With the Pathogenesis of Bovine Rotavirus Strain Circulated in Chinese Calves.Frontiers in microbiology · 2022Article
- Transcriptome sequencing reveals differences between leydig cells and sertoli cells of yak.Frontiers in veterinary science · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
backgroundThe number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets.
methodsStreptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA-mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage.
resultsUsing second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA-mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies.
conclusionsmiRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.
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