Sains Malaysiana 53(11)(2024): 3663-3672

http://doi.org/10.17576/jsm-2024-5311-10

 

Intestinal Piezo1 Promotes Neuroinflammation to Facilitate Oligodendrocyte Ferroptosis Post-Traumatic Brain Injury

(Usus Piezo1 Menggalakkan Keradangan Neuro untuk Memudahkan Oligodendrocyte Ferroptosis Kecederaan Otak Pasca Traumatik)

 

DING ZHI JUN1, WU LIANG1, CHEN ZHENG XIONG1, ZENG RUI MAO1, SHANGYUAN WANG2 & TANG MING ZHANG2,*

 

1Department of Neurosurgery Department, Ningde Municipal Hospital of Ningde Normal University, Fujian, China

2Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

 

Received 20 August 2024/Accepted 23 September 2024

 

Abstract

The coexistence of traumatic brain injury (TBI) and cognitive impairment is increasingly common in clinical practice, but current research on identifying biomarkers for such conditions and precise intervention points is insufficient. This study utilized bioinformatics analysis with paired samples to explore potential causal links between inflammatory factors and TBI and cognitive impairment. By constructing a TBI model with Piezo1 gene knockout, we assessed the activation status of microglia in the brain, the differentiation process of oligodendrocyte precursor cells. The study identified a series of inflammatory factors significantly associated with TBI, including C-C motif chemokine 19, C-X-C motif chemokine 5, and interleukin-5. Bioinformatics analysis showed increased expression of CXCL10, CCL2, GNA15, NFKB1, and the top 5 key nodes were identified using the Cytohubba plugin. The experimental results indicated that the knockout of the Piezo1 gene significantly reduced the infiltration of microglia and neuroinflammation in the brain.

 

Keywords: Bioinformatics; CXCL10; neuroinflammation; traumatic brain injury

 

Abstrak

Kewujudan kecederaan otak traumatis (TBI) dan gangguan kognitif semakin menjadi kebiasaan dalam amalan klinikal, tetapi penyelidikan semasa mengenai pengenalpastian penanda biologi untuk keadaan sedemikian dan titik intervensi yang tepat adalah tidak mencukupi. Kajian ini menggunakan analisis bioinformatik dan randomisasi Mendelian (MR) dengan sampel bersama untuk meneroka hubungan kausal berpotensi antara faktor inflamasi dengan TBI dan gangguan kognitif. Dengan membina model TBI dengan penutupan gen Piezo1, kami menilai status pengaktifan mikroglia dalam otak, proses pembezaan sel-sel pendahulu oligodendrosit. Kajian mengenal pasti siri faktor inflamasi yang signifikan berkaitan dengan TBI, termasuk kemokina motif C-C 19, kemokina motif C-X-C 5 dan interleukin-5. Analisis bioinformatik menunjukkan peningkatan ekspresi CXCL10, CCL2, GNA15, NFKB1 dan 5 nod kunci teratas dikenal pasti menggunakan plugin Cytohubba. Keputusan uji kaji menunjukkan bahawa penutupan gen Piezo1 secara signifikan mengurangkan infiltrasi mikroglia dalam otak dan melindungi pembezaan oligodendrosit.

 

Kata kunci: Bioinformatik; CXCL10; kecederaan otak traumatis; keradangan neuro

 

REFERENCES

Chen, M., Wang, H., Chen, P., Zhu, G., Li, S., Li, Z., Liu, X., Ye, G. & Chen, W. 2024a. Neonatal microglia transplantation at early stage but not late stage after traumatic brain injury shows protective effects in mice. J. Neurophysiol. 131(4): 598-606. doi:10.1152/jn.00006.2024

Chen, X., Ren, Y., Xie, P., Lei, Q. & Lu, W. 2024b. GM130-silencing may aggravate blood-brain barrier damage and affect microglia polarization by down-regulating PD-L1 expression after experimental intracerebral hemorrhage. Mol. Biol. Rep. 51(1): 919. doi:10.1007/s11033-024-09859-x

Czerpaniak, K., do Nascimento, L.F., Guo, T., Zhang, J., Liu, X., Sarzaeim, M., Fine, Z.D. & Cao, Y.Q. 2024. Low-dose interleukin-2 reverses traumatic brain injury-induced cognitive deficit and pain in a murine model. Ann. Neurol. 96(3): 508-525. doi:10.1002/ana.26998

Dvorak, P., Hlavac, V., Hanicinec, V., Rao, B.H. & Soucek, P. 2024. Genes divided according to the relative position of the longest intron show increased representation in different KEGG pathways. BMC Genomics 25: 649. doi:10.1186/s12864-024-10558-x

Fujisawa, H., Watanabe, T., Komine, O., Fuse, S., Masaki, M., Iwata, N., Murao, N., Seino, Y., Takeuchi, H, Yamanaka, K., Sawada, M., Suzuki, A. & Sugimura, Y. 2024. Prolonged extracellular low sodium concentrations and subsequent their rapid correction modulate nitric oxide production dependent on NFAT5 in microglia. Free Radic. Biol. Med. 223: 458-472. doi:10.1016/j.freeradbiomed.2024.08.019

Hayashi, H., Mak, T.W., Tanaka, Y., Kubo, Y., Izumida, M., Urae, R. & Matsuyama, T. 2024. Development of a highly sensitive platform for protein-protein interaction detection and regulation of T cell function. Proc. Natl. Acad. Sci. U.S.A. 121(33): e2318190121. doi:10.1073/pnas.2318190121

Hiwase, A. D., Ovenden, C. D., Kaukas, L. M., Finnis, M., Zhang, Z., O'Connor, S., Foo, N., Reddi, B., Wells, A.J. & Ellis, D.Y. 2024. Can rotational thromboelastometry rapidly identify theragnostic targets in isolated traumatic brain injury? Emerg. Med. Australas. doi:10.1111/1742-6723.14480

King, J., Friend, C., Zhang, D. & Carr, W. 2024. Comparative performance of three eye-tracking devices in detection of mild traumatic brain injury in acute versus chronic subject populations. Mil. Med. 189(Supplement_3): 628-635. doi:10.1093/milmed/usae205

Li, Z., Yu, S., Li, L., Zhou, C., Wang, L., Tang, S., Gu, N., Zhang, Z., Huang, Z., Chen, H., Tang, W., Wang, Y., Yang, X., Sun, X. & Yan, J. 2024. TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia. Clin. Transl. Med. 14(4): e1665. doi:10.1002/ctm2.1665

Ma, X., Liao, Z., Tan, H., Wang, K., Feng, C., Xing, P., Zhang, X., Hua, J., Jiang, P., Peng, S., Lin, H., Liang, W. & Gao, X. 2024. The association between cytomegalovirus infection and neurodegenerative diseases: A prospective cohort using UK Biobank data. EClinicalMedicine 74: 102757. doi:10.1016/j.eclinm.2024.102757

Malarkey, M.E., Fu, A.J., Mannan, N., Shaw, O.M., Haight, T.J., Cota, M.R., Jahed, N.C., Werner, J.K. & Brody, D.L. 2024. Internet-guided cognitive behavioral therapy for insomnia among patients with traumatic brain injury: A randomized clinical trial. JAMA Netw. Open 7(7): e2420090. doi:10.1001/jamanetworkopen.2024.20090

Metry, Y., McMullan, C., Upthegrove, R., Belli, A., Gomes, R.S.M., Blanch, R.J. & Ahmed, Z. 2024. Understanding how traumatic brain injury-related changes in fluid biomarkers affect quality of life outcomes in veterans: A prospective observational trial protocol (UNTANGLE). BMJ Open 14(8): e084818. doi:10.1136/bmjopen-2024-084818

Minea, H., Singeap, A.M., Minea, M., Juncu, S., Muzica, C., Sfarti, C.V., Girleanu, I., Chiriac, S., Miftode, I.D., Stanciu, C. & Trifan, A. 2024. The contribution of genetic and epigenetic factors: An emerging concept in the assessment and prognosis of inflammatory bowel diseases. Int. J. Mol. Sci. 25(15): 8420. doi:10.3390/ijms25158420

Oduro-Kwateng, E., Ali, M., Kehinde, I.O., Zhang, Z. & Soliman, M.E.S. 2024. De novo rational design of peptide-based protein-protein inhibitors (Pep-PPIs) approach by mapping the interaction motifs of the PP interface and physicochemical filtration: A case on p25-Cdk5-mediated neurodegenerative diseases. J. Cell Biochem. 125(9): e30633. doi:10.1002/jcb.30633

Ouyang, A., Chen, T., Feng, Y., Zou, J., Tu, S., Jiang, M., Sun, H. & Zhou, H. 2024. The hemagglutinin of influenza A virus induces ferroptosis to facilitate viral replication. Adv. Sci. (Weinh) 11(39): e2404365. doi:10.1002/advs.202404365

Rajkumar, R.P. 2024. Revisiting a hypothesis: The neurovascular unit as a link between major depression and neurodegenerative disorders. Front Cell Neurosci. 18: 1455606. doi:10.3389/fncel.2024.1455606

Rapport, L.J., Kalpakjian, C.Z., Sander, A.M., Lequerica, A.H., Bushnik, T., Quint, E.H. & Hanks, R.A. 2024. Menopause and traumatic brain injury: A NIDILRR collaborative TBI model systems study. Arch. Phys. Med. Rehabil. doi:10.1016/j.apmr.2024.07.021

Sok, S.P.M., Pipkin, K., Popescu, N.I., Reidy, M., Li, B., Van Remmen, H., Kinter, M., Sun, X.H., Fan, Z. & Zhao, M. 2024. Gpx4 regulates invariant NKT cell homeostasis and function by preventing lipid peroxidation and ferroptosis. J. Immunol. 213(7): 941-951. doi:10.4049/jimmunol.2400246

Xu, Y., Xu, J., Zhu, Y., Mao, H., Li, J., Kong, X., Zhu, X. & Zhang, J. 2024. Investigating gut microbiota-blood and urine metabolite correlations in early sepsis-induced acute kidney injury: Insights from targeted KEGG analyses. Front Cell Infect. Microbiol. 14: 1375874. doi:10.3389/fcimb.2024.1375874

Zhang, X., Shao, S., Song, N., Yang, B., Liu, F., Tong, Z., Wang, F. & Li, J. 2024. Integrated omics characterization reveals reduced cancer indicators and elevated inflammatory factors after thermal ablation in non-small cell lung cancer patients. Respir. Res. 25(1): 309. doi:10.1186/s12931-024-02917-9

 

*Corresponding author; email: 350571178@qq.com

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

previous next