The Journal of Practical Medicine >
TA⁃siRNA nanogel targets to inhibit Gzmb gene expression in Schwann cells of PNI and promote nerve repair
Received date: 2024-02-01
Online published: 2024-04-19
Objective To constructed a TA-siRNA nanogel to target the inhibition of Schwann cell death. Methods The study used the transcriptome sequencing data of GEO database GSE244328 for bioinformatics analysis to screen pyroptosis-related genes and evaluated the expression level of specific genes through polymerase chain reaction and protein imprint analysis. Mouse Schwann cells from the American ATCC were used， and LPS was used to simulate inflammatory stimulation. Self-assembled TA-siRNA nanogels were prepared， and CCK8 kit experiments， cytoskeleton staining， and scratch experiments were used to evaluate the cell function of TA-siRNA nanogels. GraphPad Prism 8， ImageJ， and R 4.2.1 were used for statistical difference analysis， with P < 0.05 as the statistical difference standard. Results The Gzmb gene was significantly （P < 0.05） highly expressed during the pyroptosis of Schwann cells. TA-siRNA nanogel had excellent biocompatibility with a size of 68.65 ± 7.35 nm and a potential of -36.48 mV， which could be effectively internalized by Schwann cells and did not lead to the elongation and deformation of Schwann cells （P > 0.05）. TA-siRNA nanogel could effectively inhibit the Gzmb gene of Schwann cells， thus inhibiting the death of Schwann cells and increasing the survival rate and activity of Schwann cells （P < 0.05）. Conclusion Given the role of Schwann cells in PNI， TA-siRNA nanogel inhibition of Schwann cell pyroptosis may be a potential treatment strategy for PNI in the future.
Key words： peripheral nerve injury; Schwann cells; nanogel
Jun YANG , Zhaofeng LIU , Siyuan XIE , Hanjun QIN , Yuhua ZHU , Jun. WU . TA⁃siRNA nanogel targets to inhibit Gzmb gene expression in Schwann cells of PNI and promote nerve repair[J]. The Journal of Practical Medicine, 2024 , 40(8) : 1101 -1107 . DOI: 10.3969/j.issn.1006-5725.2024.08.014
| 1 | PAN B， HUO T， HU Y， et al. Exendin-4 Promotes Schwann Cell Proliferation and Migration via Activating the Jak-STAT Pathway after Peripheral Nerve Injury ［J］. Neuroscience， 2020， 437： 1-10. doi:10.1016/j.neuroscience.2020.04.017 |
| 2 | WANG J， LU S， YUAN Y， et al. Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats ［J］. Mediators Inflamm， 2023， 2023： 9721375. doi:10.1155/2023/9721375 |
| 3 | ELSAYED H， FARONI A， ASHRAF M R， et al. Development and Characterisation of an in vitro Model of Wallerian Degeneration ［J］. Front Bioeng Biotechnol， 2020， 8： 784. doi:10.3389/fbioe.2020.00784 |
| 4 | CHEN C Y， RAO S S， REN L， et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis ［J］. Theranostics， 2018， 8（6）： 1607-1623. doi:10.7150/thno.22958 |
| 5 | DYKXHOORN D M， PALLISER D， LIEBERMAN J. The silent treatment： siRNAs as small molecule drugs ［J］. Gene Ther， 2006， 13（6）： 541-552. doi:10.1038/sj.gt.3302703 |
| 6 | EVERETT E， MATHIOUDAKIS N. Update on management of diabetic foot ulcers ［J］. Ann N Y Acad Sci， 2018， 1411（1）： 153-165. doi:10.1111/nyas.13569 |
| 7 | BLOOM D E， BLACK S， SALISBURY D， et al. Antimicrobial resistance and the role of vaccines ［J］. Proc Natl Acad Sci U S A， 2018， 115（51）： 12868-12871. doi:10.1073/pnas.1717157115 |
| 8 | OH Y K， PARK T G. siRNA delivery systems for cancer treatment ［J］. Adv Drug Deliv Rev， 2009， 61（10）： 850-862. doi:10.1016/j.addr.2009.04.018 |
| 9 | HAUPENTHAL J， BAEHR C， KIERMAYER S， et al. Inhibition of RNAse A family enzymes prevents degradation and loss of silencing activity of siRNAs in serum ［J］. Biochem Pharmacol， 2006， 71（5）： 702-710. doi:10.1016/j.bcp.2005.11.015 |
| 10 | NAKAGAWA O， MING X， HUANG L， et al. Targeted intracellular delivery of antisense oligonucleotides via conjugation with small-molecule ligands ［J］. J Am Chem Soc， 2010， 132（26）： 8848-8849. doi:10.1021/ja102635c |
| 11 | GOLDMAN M J， CRAFT B， HASTIE M， et al. Visualizing and interpreting cancer genomics data via the Xena platform ［J］. Nat Biotechnol， 2020， 38（6）： 675-678. doi:10.1038/s41587-020-0546-8 |
| 12 | SUNDARAM V K， SCHüTZA V， SCHR?TER N H， et al. Adipo-glial signaling mediates metabolic adaptation in peripheral nerve regeneration ［J］. Cell Metab， 2023， 35（12）： 2136-2152.e9. doi:10.1016/j.cmet.2023.10.017 |
| 13 | RITCHIE M E， PHIPSON B， WU D， et al. limma powers differential expression analyses for RNA-sequencing and microarray studies ［J］. Nucleic Acids Res， 2015， 43（7）： e47. doi:10.1093/nar/gkv007 |
| 14 | YU G， WANG L G， HAN Y， et al. clusterProfiler： an R package for comparing biological themes among gene clusters ［J］. Omics， 2012， 16（5）： 284-287. doi:10.1089/omi.2011.0118 |
| 15 | 孙悦，戈娜，赵雪 等.沙棘熊果酸对大鼠坐骨神经损伤修复作用［J］.实用医学杂志，2023，39（24）：3158-3162. doi:10.3969/j.issn.1006-5725.2023.24.002 |
| 16 | 肖海丽，袁真，魏超，等. 施万细胞可塑性和自噬对周围神经损伤修复的作用 ［J］. 南昌大学学报（医学版）， 2023， 63（5）： 87-91. |
| 17 | 高曌， 骆天炯， 宣思，等. 施万细胞在周围神经疾病中的免疫调节研究进展 ［J］. 现代医药卫生， 2023， 39（2）： 313-319. doi:10.3969/j.issn.1009-5519.2023.02.029 |
| 18 | CHEN Y， MENG J， BI F， et al. Corrigendum： NEK7 Regulates NLRP3 Inflammasome Activation and Neuroinflammation Post-traumatic Brain Injury ［J］. Front Mol Neurosci， 2019， 12： 247. doi:10.3389/fnmol.2019.00247 |
| 19 | WU C， LU W， ZHANG Y， et al. Inflammasome Activation Triggers Blood Clotting and Host Death through Pyroptosis ［J］. Immunity， 2019， 50（6）： 1401-1411.e4. doi:10.1016/j.immuni.2019.04.003 |
| 20 | ROGERS C， ERKES D A， NARDONE A， et al. Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation ［J］. Nat Commun， 2019， 10（1）： 1689. doi:10.1038/s41467-019-09397-2 |
| 21 | LI Z F， WANG Y C， FENG Q R， et al. Inhibition of the C3a receptor attenuates sepsis-induced acute lung injury by suppressing pyroptosis of the pulmonary vascular endothelial cells ［J］. Free Radic Biol Med， 2022， 184： 208-217. doi:10.1016/j.freeradbiomed.2022.02.032 |
| 22 | CAI Z， YUAN S， LUAN X， et al. Pyroptosis-Related Inflammasome Pathway： A New Therapeutic Target for Diabetic Cardiomyopathy ［J］. Front Pharmacol， 2022， 13： 842313. doi:10.3389/fphar.2022.842313 |
| 23 | DUEWELL P， KONO H， RAYNER K J， et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals ［J］. Nature， 2010， 464（7293）： 1357-1361. doi:10.1038/nature08938 |
| 24 | MENG Q， LI Y， JI T， et al. Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy ［J］. J Adv Res， 2021， 28： 149-164. doi:10.1016/j.jare.2020.08.010 |
| 25 | QIJUN Z， HUAN Z， LING G， et al. The levels and significance of inflammasomes in the mouse retina following optic nerve crush ［J］. Int Immunopharmacol， 2019， 71： 313-320. doi:10.1016/j.intimp.2019.03.029 |
| 26 | CHEN S， ZUO Y， HUANG L， et al. The MC（4） receptor agonist RO27-3225 inhibits NLRP1-dependent neuronal pyroptosis via the ASK1/JNK/p38 MAPK pathway in a mouse model of intracerebral haemorrhage ［J］. Br J Pharmacol， 2019， 176（9）： 1341-1356. doi:10.1111/bph.14639 |
| 27 | HAN C， YANG Y， GUAN Q， et al. New mechanism of nerve injury in Alzheimer's disease： β-amyloid-induced neuronal pyroptosis ［J］. J Cell Mol Med， 2020， 24（14）： 8078-8090. doi:10.1111/jcmm.15439 |
| 28 | TAO Y， WANG F， XU Z， et al. Gasdermin D in peripheral nerves： the pyroptotic microenvironment inhibits nerve regeneration ［J］. Cell Death Discov， 2021， 7（1）： 144. doi:10.1038/s41420-021-00529-6 |
| 29 | LEI H， FAN D. A Combination Therapy Using Electrical Stimulation and Adaptive， Conductive Hydrogels Loaded with Self-Assembled Nanogels Incorporating Short Interfering RNA Promotes the Repair of Diabetic Chronic Wounds ［J］. Adv Sci （Weinh）， 2022， 9（30）： e2201425. doi:10.1002/advs.202201425 |
| 30 | 范磊. 电活性水凝胶的构建及其在神经损伤修复中的应用 ［D］. 广州：华南理工大学， 2021. |
| 31 | 刘尧. 透明质酸/单宁酸复合动态多功能水凝胶用于周围神经损伤修复的研究 ［D］. 长春：吉林大学， 2023. |
/
| 〈 |
|
〉 |