دورية أكاديمية
Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome
| العنوان: | Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome |
|---|---|
| المؤلفون: | Srivastava, Tarak, Garola, Robert E., Zhou, Jianping, Boinpelly, Varun C., Rezaiekhaligh, Mohammad H., Joshi, Trupti, Jiang, Yuexu, Ebadi, Diba, Sharma, Siddarth, Sethna, Christine, Staggs, Vincent S., Sharma, Ram, Gipson, Debbie S., Hao, Wei, Wang, Yujie, Mariani, Laura H., Hodgin, Jeffrey B., Rottapel, Robert, Yoshitaka, Teruhito, Ueki, Yasuyoshi, Sharma, Mukut |
| المساهمون: | Biomedical Sciences and Comprehensive Care, School of Dentistry |
| المصدر: | PMC |
| بيانات النشر: | American Society for Clinical Investigation |
| سنة النشر: | 2024 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Nephrology, Innate immunity, Kidney glomerulus |
| الوصف: | Despite clinical use of immunosuppressive agents, the immunopathogenesis of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remains unclear. Src homology 3-binding protein 2 (SH3BP2), a scaffold protein, forms an immune signaling complex (signalosome) with 17 other proteins, including phospholipase Cγ2 (PLCγ2) and Rho-guanine nucleotide exchange factor VAV2 (VAV2). Bioinformatic analysis of human glomerular transcriptome (Nephrotic Syndrome Study Network cohort) revealed upregulated SH3BP2 in MCD and FSGS. The SH3BP2 signalosome score and downstream MyD88, TRIF, and NFATc1 were significantly upregulated in MCD and FSGS. Immune pathway activation scores for Toll-like receptors, cytokine-cytokine receptor, and NOD-like receptors were increased in FSGS. Lower SH3BP2 signalosome score was associated with MCD, higher estimated glomerular filtration rate, and remission. Further work using Sh3bp2KI/KI transgenic mice with a gain-in-function mutation showed ~6-fold and ~25-fold increases in albuminuria at 4 and 12 weeks, respectively. Decreased serum albumin and unchanged serum creatinine were observed at 12 weeks. Sh3bp2KI/KI kidney morphology appeared normal except for increased mesangial cellularity and patchy foot process fusion without electron-dense deposits. SH3BP2 co-immunoprecipitated with PLCγ2 and VAV2 in human podocytes, underscoring the importance of SH3BP2 in immune activation. SH3BP2 and its binding partners may determine the immune activation pathways resulting in podocyte injury leading to loss of the glomerular filtration barrier. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | JCI Insight; Srivastava T, Garola RE, Zhou J, et al. Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome. JCI Insight. 2024;9(3):e170055. Published 2024 Feb 8. doi:10.1172/jci.insight.170055; https://hdl.handle.net/1805/41812Test |
| الإتاحة: | https://doi.org/10.1172/jci.insight.170055Test https://hdl.handle.net/1805/41812Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.3E8E2EF9 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |