ArticleExperimental & molecular medicine2022
Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Efficacy of vacuum erectile device in refractory erectile dysfunction: a systematic review and meta-analysis.International journal of impotence research · 2026Pooled it
- Review
- Slit2/Robo Signaling Restores Diabetic Erectile Function via Neurovascular Remodeling.Andrology · 2026Article
- A polymer that reinforces luminal barrier function and attenuates inflammation in murine colitis.Research square · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy.Cellular & molecular immunology · 2026Article
- Novel copper-ion coordinated andrographolide-loaded hydrogel activates Rac1/JNK1 axis for enhancing diabetic wound healing.NPJ Regenerative medicine · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Brucein D suppresses breast cancer proliferation and migration via targeting the FAK/LRG1 signaling pathway.Scientific reports · 2025Article
- Integrative transcriptomic and genomic insights into diabetic kidney disease: evidence from multi-omics analysis and experimental validation.Renal failure · 2025Article
- Exogenous administration of heparin-binding epidermal growth factor-like growth factor improves erectile function in mice with bilateral cavernous nerve injury.Asian journal of andrology · 2025Article
- Dimethyl Fumarate Improves Diabetic Erectile Dysfunction in Rats via Nrf2-Mediated Suppression of Penile Endothelial Oxidative Stress.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Gut Microbial Metabolite Imidazole Propionate Impairs Endothelial Cell Function and Promotes the Development of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Covalent functionalization of G protein-coupled receptors by small molecular probes.RSC chemical biology · 2025Review
- Diet-enhanced LRG1 expression promotes insulin hypersecretion and ER stress in pancreatic beta cells.Diabetologia · 2025Article
- MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2.Experimental & molecular medicine · 2025Article
- Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration.Investigative and clinical urology · 2025Article
- Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.Investigative and clinical urology · 2024Article
- Article
- Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress.Heliyon · 2024Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM. Here, we found that the adhesion GPCR latrophilin-2 (LPHN2) is a TGF-β-independent receptor of LRG1. By interacting with LPHN2, LRG1 promotes both angiogenic and neurotrophic processes in mouse tissue explants under hyperglycemic conditions. Preclinical studies in a diabetic ED mouse model showed that LRG1 administration into the penile tissue, which exhibits significantly increased LPHN2 expression, fully restores erectile function by rescuing vascular and neurological abnormalities. Further investigations revealed that PI3K, AKT, and NF-κB p65 constitute the key intracellular signaling pathway of the LRG1/LPHN2 axis, providing important mechanistic insights into LRG1-mediated angiogenesis and nerve regeneration in DM. Our findings suggest that LRG1 can be a potential new therapeutic option for treating aberrant peripheral blood vessels and neuropathy associated with diabetic complications, such as diabetic ED.
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