CXCR4 regulates macrophage M1 polarization by altering glycolysis to promote prostate fibrosis
In this study, we demonstrated that reducing CXCR4 expression during LPS treatment of macrophages can alleviate M1 polarization. Silencing CXCR4 can inhibit glycolytic metabolism, enhance mitochondrial function, and promote macrophage transition from M1 to M2. Additionally, in vivo functional experiments using AAV carrying CXCR4 showed that blocking CXCR4 in experimental autoimmune prostatitis (EAP) can alleviate inflammation and experimental prostate fibrosis development. Mechanistically, CXCR4, a chemokine receptor, when silenced, weakens the PI3K/AKT/mTOR pathway as its downstream signal, reducing c-MYC expression. PFKFB3, a key enzyme involved in glucose metabolism, is a target gene of c-MYC, thus impacting macrophage polarization and glycolytic metabolism processes.
Authors
- Wei Peng (ORCID: https://orcid.org/0000-0002-5780-2157)
- Xianguo Chen (ORCID: https://orcid.org/0000-0001-8819-9373)
- Chang Yin Liang (ORCID: https://orcid.org/0000-0003-2317-1323)
- Jian Song (ORCID: https://orcid.org/0000-0001-5850-025X)
- Jing Chen (ORCID: https://orcid.org/0000-0003-2434-0010)
- Meng Tong (ORCID: https://orcid.org/0000-0003-4832-2490)
- Rui Feng (ORCID: https://orcid.org/0000-0003-0861-443X)
- Wenlong Xu (ORCID: https://orcid.org/0009-0003-4850-0768)
- Wenming Ma
- Chen Zhang (ORCID: https://orcid.org/0000-0001-8706-1372)
- Yi Zhang (ORCID: https://orcid.org/0000-0001-6223-4724)
Institutions
- Anhui Medical University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Shuguang Hospital (CN)
Publication Details
- Journal
- Cell Communication and Signaling
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1186/s12964-024-01828-y
- Citations
- 25
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 6.01