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SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells

التفاصيل البيبلوغرافية
العنوان: SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells
المؤلفون: Kim, Ji Young, Bai, Yuntao, Jayne, Laura A, Abdulkader, Ferdos, Gandhi, Megha, Perreau, Tayla, Parikh, Samir V, Gardner, David S, Davidson, Alan J, Sander, Veronika, Song, Min-Ae, Bajwa, Amandeep, Pabla, Navjot Singh
بيانات النشر: American Society for Biochemistry & Molecular Biology (ASBMB)
سنة النشر: 2020
المجموعة: University of Auckland Research Repository - ResearchSpace
مصطلحات موضوعية: 03 Chemical Sciences, 06 Biological Sciences, 11 Medical and Health Sciences
الوصف: Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, as well as cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxia, cytotoxicity, and inflammatory insults to renal tubular epithelial cells (RTECs) resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI. We find that Vgf nerve growth factor inducible gene upregulation is a common transcriptional stress response in RTECs to ischemia, cisplatin, and rhabdomyolysis-associated renal injury. The Vgf gene encodes a secretory peptide precursor protein that has critical neuro-endocrine functions; however, its role in the kidneys remains unknown. Our functional studies show that RTEC-specific Vgf gene ablation exacerbates ischemia, cisplatin, and rhabdomyolysis-associated AKI in vivo and cisplatin-induced RTEC cell death in vitro. Importantly, aggravation of cisplatin-induced renal injury caused by Vgf gene ablation is partly reversed by TLQP-21, a Vgf-derived peptide. Finally, in vitro and in vivo mechanistic studies showed that injury-induced Vgf upregulation in RTECs is driven by the transcriptional regulator Sox9. These findings reveal a crucial downstream target of the Sox9-directed transcriptional program and identify Vgf as a stress-responsive protective gene in kidney tubular epithelial cells.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 0021-9258
1083-351X
العلاقة: Journal of Biological Chemistry; http://hdl.handle.net/2292/54007Test
DOI: 10.1074/jbc.ra120.015110
الإتاحة: https://doi.org/10.1074/jbc.ra120.015110Test
http://hdl.handle.net/2292/54007Test
حقوق: Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. ; https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmTest ; Copyright: The author ; http://purl.org/eprint/accessRights/RestrictedAccessTest
رقم الانضمام: edsbas.A56EE9B6
قاعدة البيانات: BASE
الوصف
تدمد:00219258
1083351X
DOI:10.1074/jbc.ra120.015110