Scholarlink

Background <p>One of the main reasons of disability and death is stroke in China and other countries, with growing evidence pointing to the role of microglial polarization in its pathogenesis. Epidermal growth factor receptor as well as Glycoprotein non-metastatic melanoma protein have been implicated in cellular signaling pathways relevant to microglial function. However, the mechanism by which GPNMB regulates EGFR signaling and its impact on mitochondrial translocation and polarization remains unclear.</p> Methods <p>We established middle cerebral artery occlusion model in mice to investigate GPNMB expression and its role in microglial activation. Various experimental techniques, including TTC staining, western blotting, Nissl staining, H&amp;E staining, immunofluorescence, and flow cytometry, were employed to assess cellular changes and molecular interactions. Furthermore, the effects of GPNMB on energy metabolism were evaluated through ATP assays and mitochondrial membrane potential assessments.</p> Results <p>Upregulated GPNMB was observed in microglia following MCAO. GPNMB Inhibition resulted in reduced infarct volume, diminished neuronal damage, and altered microglial polarization towards the anti-inflammation phenotype. Additionally, GPNMB was found to regulate EGFR translocation, which in turn influenced HK2 expression, thereby affecting mitochondrial function and energy metabolism in microglia. Expression of respiratory-chain proteins (CYTB, MTCO2, ATP6) was increased following GPNMB inhibition. The use of EGFR activators and inhibitors further confirmed the critical role of this signaling pathway in mediating GPNMB's effects.</p> Conclusion <p>In conclusion, GPNMB regulates mitochondrial translocation of ERGR via HK2, influencing microglial respiratory chain and metabolic defects to promote stroke progression.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

GPNMB regulates EGFR mitochondrial translocation via HK2, influencing microglial respiratory chain and metabolic defects to promote polarization and stroke progression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月25日

查看全文
  • Chang Gao,
  • Qiong Nie,
  • Yongnan Hao,
  • Hongqiang Song,
  • Cui-Cui Zhang

摘要

Background

One of the main reasons of disability and death is stroke in China and other countries, with growing evidence pointing to the role of microglial polarization in its pathogenesis. Epidermal growth factor receptor as well as Glycoprotein non-metastatic melanoma protein have been implicated in cellular signaling pathways relevant to microglial function. However, the mechanism by which GPNMB regulates EGFR signaling and its impact on mitochondrial translocation and polarization remains unclear.

Methods

We established middle cerebral artery occlusion model in mice to investigate GPNMB expression and its role in microglial activation. Various experimental techniques, including TTC staining, western blotting, Nissl staining, H&E staining, immunofluorescence, and flow cytometry, were employed to assess cellular changes and molecular interactions. Furthermore, the effects of GPNMB on energy metabolism were evaluated through ATP assays and mitochondrial membrane potential assessments.

Results

Upregulated GPNMB was observed in microglia following MCAO. GPNMB Inhibition resulted in reduced infarct volume, diminished neuronal damage, and altered microglial polarization towards the anti-inflammation phenotype. Additionally, GPNMB was found to regulate EGFR translocation, which in turn influenced HK2 expression, thereby affecting mitochondrial function and energy metabolism in microglia. Expression of respiratory-chain proteins (CYTB, MTCO2, ATP6) was increased following GPNMB inhibition. The use of EGFR activators and inhibitors further confirmed the critical role of this signaling pathway in mediating GPNMB's effects.

Conclusion

In conclusion, GPNMB regulates mitochondrial translocation of ERGR via HK2, influencing microglial respiratory chain and metabolic defects to promote stroke progression.

Graphical Abstract