Aberrant regulation of retinoic acid signaling genes in cerebral arterio venous malformation nidus and neighboring astrocytes
| العنوان: | Aberrant regulation of retinoic acid signaling genes in cerebral arterio venous malformation nidus and neighboring astrocytes |
|---|---|
| المؤلفون: | Jaya Mary Thomas, Mathew Abraham, Arumugam Rajavelu, Sumi Surendran, Chandrasekharan C Kartha, Dhakshmi Sasankan |
| المصدر: | Journal of Neuroinflammation, Vol 18, Iss 1, Pp 1-13 (2021) Journal of Neuroinflammation |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Intracranial Arteriovenous Malformations, Male, Pathology, medicine.medical_specialty, Immunology, Short Report, Retinoic acid, Tretinoin, Vimentin, Biology, lcsh:RC346-429, ALDH1A2, Pathogenesis, Transcriptome, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Gene expression, medicine, Humans, lcsh:Neurology. Diseases of the nervous system, Neovascularization, Pathologic, General Neuroscience, Gene Expression Regulation, Neurology, chemistry, Vascular system, Astrocytes, Arteriovenous Fistula, biology.protein, Immunohistochemistry, Female, Immunostaining, Signal Transduction |
| الوصف: | Background Cerebral arterio venous malformations (AVM) are a major causal factor for intracranial hemorrhage, which result in permanent disability or death. The molecular mechanisms of AVM are complex, and their pathogenesis remains an enigma. Current research on cerebral AVM is focused on characterizing the molecular features of AVM nidus to elucidate the aberrant signaling pathways. The initial stimuli that lead to the development of AVM nidus structures between a dilated artery and a vein are however not known. Methods In order to understand the molecular basis of development of cerebral AVM, we used in-depth RNA sequencing with the total RNA isolated from cerebral AVM nidus. Immunoblot and qRT-PCR assays were used to study the differential gene expression in AVM nidus, and immunofluorescence staining was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues. Immunohistochemistry was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues. Results The transcriptome study has identified 38 differentially expressed genes in cerebral AVM nidus, of which 35 genes were upregulated and 3 genes were downregulated. A final modular analysis identified an upregulation of ALDH1A2, a key rate-limiting enzyme of retinoic acid signaling pathway. Further analysis revealed that CYR61, a regulator of angiogenesis, and the target gene for retinoic acid signaling is upregulated in AVM nidus. We observed that astrocytes associated with AVM nidus are abnormal with increased expression of GFAP and Vimentin. Triple immunofluorescence staining of the AVM nidus revealed that CYR61 was also overexpressed in the abnormal astrocytes associated with AVM tissue. Conclusion Using high-throughput RNA sequencing analysis and immunostaining, we report deregulated expression of retinoic acid signaling genes in AVM nidus and its associated astrocytes and speculate that this might trigger the abnormal angiogenesis and the development of cerebral AVM in humans. |
| تدمد: | 1742-2094 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c42a7139c49123df1aef2f60c8cc31bTest https://doi.org/10.1186/s12974-021-02094-2Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7c42a7139c49123df1aef2f60c8cc31b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17422094 |
|---|