ArticleNature communications2022
Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- CanInternational journal of molecular sciences · 2026Article
- PUM1 and PUM2 promote translation of chromatin regulators to ensure mammalian spermatogenesis.Science advances · 2026Article
- Context‑dependent duality of the apelin/elabela‑APJ system in diabetes and its complications (Review).International journal of molecular medicine · 2026Review
- The relationships between diabetic male infertility, diabetic cognitive impairment, and the neuroendocrine-immune network: A review.Medicine · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Endothelial PDGF Signaling Dysregulation Impairs Testicular Interstitial Homeostasis in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ALKBH5 facilitates Srgn stability via m6A demethylation to disrupt blood-testis barrier integrity in the high-fat diet mice.Cellular and molecular life sciences : CMLS · 2026Article
- Inflammation-Driven Remodeling of the Blood-Testis Barrier: Roles of Junctional Complexes, Actin Dynamics, and Kinase Signaling.Biomedicines · 2026Review
- Benign Uroandrological Ecosystem: A Thorough Overview from Single-Cell and Spatial Transcriptomics.Research (Washington, D.C.) · 2026Review
- Article
- Integrative bioinformatics and experiments identify RIBC2 as a key regulator in the esophageal cancer.PloS one · 2026Article
- Atorvastatin improves spermatogenesis in murine and in vitro human chronic orchitis models through restoring blood-testis barriers.Cell death discovery · 2025Article
- Mechanistic insights into targeting APLN/APJ for ameliorating testosterone deficiency and reproductive disorders in diabetic mice.Cell communication and signaling : CCS · 2025Article
- Multi-Omics Profiling Identifies Apolipoprotein E as an Important Regulator of Steroidogenesis in Bactrian Camel Poll Glands During the Breeding Season.Animals : an open access journal from MDPI · 2025Article
- Revealing the Impact of Mono(2-ethylhexyl) Phthalate (MEHP) on Prostate Cancer Based on Network Toxicology and Molecular Docking Approaches.Journal of applied toxicology : JAT · 2025Article
- Targeting APJ drives BNIP3-PINK1-PARKIN induced mitophagy and improves systemic inflammatory bone loss.Journal of advanced research · 2025Article
- Systemic impacts of diabetes on spermatogenesis and intervention strategies: multilayered mechanism analysis and cutting-edge therapeutic approaches.Reproductive biology and endocrinology : RB&E · 2025Review
- Mitochondrial Quality Control in Bovine Oocyte Maturation: Mechanisms, Challenges, and Prospects for Enhancing Reproductive Efficiency.Animals : an open access journal from MDPI · 2025Review
- Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.Acta pharmaceutica Sinica. B · 2025Article
- PCM1 orchestrates centrosomal and flagellar protein transport to promote sperm maturation.Communications biology · 2025Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus is one of the most prevalent metabolic diseases presenting with systemic pathologies, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contributing to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we perform STRT-seq to examine the transcriptome of diabetic patients' testes at single-cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure are dramatically impaired. Among these deregulate pathways, the Apelin (APLN) peptide/Apelin-receptor (APJ) axis is hyper-activated in diabetic patients' testes. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppress the production of carnitine and repress the expression of cell adhesion genes in Sertoli cells. Together, these effects culminate in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorate the BTB damage and, importantly, improve functional spermatogenesis in diabetic db/db mice. We also translate and validate these findings in cultured human testes. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients.
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