دورية أكاديمية
Targeting Src homology phosphatase 2 ameliorates mouse diabetic nephropathy by attenuating ERK/NF-κB pathway-mediated renal inflammation
| العنوان: | Targeting Src homology phosphatase 2 ameliorates mouse diabetic nephropathy by attenuating ERK/NF-κB pathway-mediated renal inflammation |
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| المؤلفون: | Che Yu, Zhuo Li, Cuili Nie, Lei Chang, Tao Jiang |
| المصدر: | Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-12 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Cytology |
| مصطلحات موضوعية: | Diabetic nephropathy, Src homology phosphatase 2, ERK/NF-κB pathway, Renal inflammation, Medicine, Cytology, QH573-671 |
| الوصف: | Abstract Renal inflammation is a pivotal mechanism underlying the pathophysiology of diabetic nephropathy (DN). The Src homology phosphatase 2 (SHP2) has been demonstrated to be linked to diabetes-induced inflammation, yet its roles and explicit molecular mechanisms in DN remain unexplored. Here, we report that SHP2 activity is upregulated in both DN patients and db/db mice. In addition, pharmacological inhibition of SHP2 with its specific inhibitor PHPS1 alleviates DN in db/db mice and attenuates renal inflammation. In vitro, PHPS1 administration prevents inflammatory responses in HK-2 cells stimulated by high glucose (HG). Mechanistically, PHPS1 represses HG-induced activation of the proinflammatory ERK/NF-κB signaling pathway, and these inhibitory effects are blocked in the presence of an ERK specific inhibitor, hence demonstrating that PHPS1 suppresses ERK/NF-κB pathway-mediated inflammation. Moreover, PHPS1 retards ERK/NF-κB pathway activation in db/db mice, and histologically, SHP2 activity is positively correlated with ERK/NF-κB activation in DN patients. Taken together, these findings identify SHP2 as a potential therapeutic target and show that its pharmacological inhibition might be a promising strategy to mitigate DN. Video Abstract |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1478-811X |
| العلاقة: | https://doaj.org/toc/1478-811XTest |
| DOI: | 10.1186/s12964-023-01394-9 |
| الوصول الحر: | https://doaj.org/article/62f6ff060560437ba167946e383b87ecTest |
| رقم الانضمام: | edsdoj.62f6ff060560437ba167946e383b87ec |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/s12964-023-01394-9 |