ArticleCell death and differentiation2018
RGMa mediates reactive astrogliosis and glial scar formation through TGFβ1/Smad2/3 signaling after stroke.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 116 citations in OpenAlex.
- Calycosin-7-O-β-D-Glucoside Facilitates Axonal Regrowth and Functional Recovery via Rho/ROCK Pathway Inhibition After Cerebral Ischemia/Reperfusion.International journal of molecular sciences · 2026Article
- MYC-driven gliosis impairs neuron-glia communication in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- TRIM21 promotes astrocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis by stabilizing RGMa via K33-linked ubiquitination.Journal of neuroinflammation · 2026Article
- Chondroitin Sulfate Proteoglycans in CNS Development and Pathophysiology.Journal of neuroscience research · 2026Review
- Identification of distinct and shared biomarker panels in different manifestations of cerebral small-vessel disease through proteomic profiling.Nature aging · 2026Article
- Spatiotemporal Double-Edged Sword of Macrophages: Temporal Regulation of Neuroinflammation and Neurorepair in Ischemic Stroke.Journal of immunology research · 2026Review
- Mechanisms and therapeutic advances of gut metabolites in the regulation of neuroimmune inflammatory diseases.Frontiers in immunology · 2026Review
- From anti-inflammation to pro-resolution: a new paradigm for specialized pro-resolving mediators in regulating neuroinflammation and repair after cerebral ischemia-reperfusion.Frontiers in immunology · 2026Review
- Unlocking the Therapeutic Potential of RGMa: A New Frontier in Neurological Disorder Treatment.Molecular neurobiology · 2025Review
- Beyond the gut: decoding the gut-immune-brain axis in health and disease.Cellular & molecular immunology · 2025Review
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- Repulsive guidance molecule A in the resolution of inflammation from ischemic stroke-associated pneumonia in mice.Scientific reports · 2025Article
- Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms.World journal of diabetes · 2025Review
- Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.medRxiv : the preprint server for health sciences · 2025Article
- Endothelium-specific endoglin triggers astrocyte reactivity via extracellular vesicles in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2025Article
- Knockdown of RGMa reduces vascular calcification by inhibiting the AKT signaling pathway.Scientific reports · 2025Article
- The Role of Astrocytes in Poststroke Rehabilitation.Brain and behavior · 2025Review
- Advancing Ischemic Stroke Prognosis: Key Role of MiR-155 Non-Coding RNA.International journal of molecular sciences · 2025Review
- Repulsive Guidance Molecule-A as a Therapeutic Target Across Neurological Disorders: An Update.International journal of molecular sciences · 2025Review
- Gastrodin inhibits reactive astrocyte-mediated inflammation in hypoxic-ischemic brain damage through S100B/RAGE-Smad3 signaling.Acta biochimica et biophysica Sinica · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to stroke, astrocytes become reactive astrogliosis and are a major component of a glial scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and glial scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and glial scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the glial scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and glial scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and glial scar formation induced by TGFβ1, including cellular hypertrophy, glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and glial scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.