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SHP2 in microglia attenuates neuroinflammation and cognitive deficits in vascular dementia by modulating the FAK/Src/PU. 1/IRF8 pathway
Yanli Jia, Yanyan Ren, Yunmei Yu, Fangming Dong, Minxia Geng, Rongfang Feng. European journal of medical research, 2026-03-31
Topic: Brain proteins, microglia and lab models
Vascular dementia is a common cognitive disorder that is often triggered by neuroinflammatory responses caused by cerebrovascular injury, which further exacerbates the progression of the disease. Microglia play an important role in neuroinflammation, and the signalling pathway within them may affect the progression of the disease. The role of SHP2 (Src homology protein-tyrosine phosphatase 2), a key signaling molecule, in microglia during VD remains unclear. This study aimed to investigate the effect and underlying mechanism of microglial SHP2 on the progression of vascular dementia. Bioinformatics analysis was employed to identify genes specifically expressed in vascular dementia. A vascular dementia (VD) model was established in male Wistar rats through bilateral carotid artery ligation. A randomized and double-blind study design was implemented throughout the experiments. Behavioral changes in the rats were assessed using the Morris water maze and open field tests. Pathological conditions in the hippocampal CA1 region were examined via HE staining, while immunohistochemical staining was utilized to detect p-SHP2 expression. Western blot, RT-qPCR, and ELISA were conducted to measure the expression levels of p-Src, p-FAK, p-JNK, p-NF-κB, NOX4, P53, PU. 1, IRF8, NLRP3, NLRC4, αvβ3 integrin, IL-1β, IFNα, IFNβ, IL-18, and β-amyloid in microglial BV2 cells. Angiogenesis assays were performed to evaluate the angiogenic capacity of BV2 cells. SHP2 exhibited specific low expression in vascular dementia. It enhanced the learning and memory abilities of rats with vascular dementia and mitigated brain tissue damage caused by the disease. Inhibition of SHP2 within microglia upregulated the expression of p-Src, p-FAK, p-JNK, p-NF-κB, NOX4, P53, PU. 1, IRF8, NLRP3, NLRC4, αvβ3 integrin, IL-1β, IFNα, IFNβ, IL-18, and β-Amyloid. However, administration of the FAK and Src inhibitor SU6656 abolished the effects of SHP2 inhibition, leading to suppressed expression of the aforementioned proteins. Additionally, SHP2 was shown to inhibit the angiogenic capacity of BV2 cells. Our findings suggest that SHP2 within microglia may inhibit the progression of vascular dementia by suppressing the FAK/Src/PU. 1/IRF8 pathway-mediated neuroinflammatory response. Targeting SHP2 could represent a potential therapeutic strategy for VD.
Key findings
- Our findings suggest that SHP2 within microglia may inhibit the progression of vascular dementia by suppressing the FAK/Src/PU. 1/IRF8 pathway-mediated neuroinflammatory response.
Why it matters
In a rat model of vascular dementia, microglial SHP2 appeared to inhibit disease progression by suppressing a neuroinflammatory signaling pathway. These are animal findings, so it is not known whether targeting SHP2 would help people with vascular dementia.
Study details
- Evidence strengthHigh
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 34 of the 96 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (European journal of medical research) |
| Journal's citation record | 1 / 4 | European journal of medical research: journal h-index 80 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Rongfang Feng holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Hebei General Hospital: institution h-index 87 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 34 of the 96 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40001-026-04317-9
- Original source →
- Free full text: European journal of medical research →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Jia, Y., Ren, Y., Yu, Y., Dong, F., Geng, M., & Feng, R. (2026). SHP2 in microglia attenuates neuroinflammation and cognitive deficits in vascular dementia by modulating the FAK/Src/PU. 1/IRF8 pathway. European journal of medical research. https://doi.org/10.1186/s40001-026-04317-9
Vancouver
Jia Y, Ren Y, Yu Y, Dong F, Geng M, Feng R. SHP2 in microglia attenuates neuroinflammation and cognitive deficits in vascular dementia by modulating the FAK/Src/PU. 1/IRF8 pathway. European journal of medical research. 2026. doi:10.1186/s40001-026-04317-9.
BibTeX
@article{jia2026-22fe2677,
author = {Jia, Yanli and Ren, Yanyan and Yu, Yunmei and Dong, Fangming and Geng, Minxia and Feng, Rongfang},
title = {{SHP2 in microglia attenuates neuroinflammation and cognitive deficits in vascular dementia by modulating the FAK/Src/PU. 1/IRF8 pathway}},
journal = {European journal of medical research},
year = {2026},
doi = {10.1186/s40001-026-04317-9},
url = {https://doi.org/10.1186/s40001-026-04317-9}
}
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