Transcriptional genes of lysosome-associated membrane protein 2A in sciatic nerve injuries by bioinformatics.


Journal

Neuroreport
ISSN: 1473-558X
Titre abrégé: Neuroreport
Pays: England
ID NLM: 9100935

Informations de publication

Date de publication:
19 Jun 2024
Historique:
medline: 27 6 2024
pubmed: 27 6 2024
entrez: 27 6 2024
Statut: aheadofprint

Résumé

Recent studies have shown that autophagy is activated in response to nerve damage and occurs simultaneously with the initial stages of Schwann cell-mediated demyelination. Although several studies have reported that macroautophagy is involved in the peripheral nerve, the role of chaperone-mediated autophagy (CMA) has not yet been investigated in peripheral nerve injury. The present study investigates the role of CMA in the sciatic nerve. Using a mouse model of sciatic nerve injury, the authors employed immunofluorescence analysis to observe the expression of LAMP2A, a critical marker for CMA. RNA sequencing was performed to observe the transcriptional profile of Lamp2a in Schwann cells. Bioinformatics analysis was carried out to observe the hub genes associated with Lamp2a. Expression of Lamp2a, a key gene in CMA, increased following sciatic nerve injury, based on an immunofluorescence assay. To identify differentially expressed genes using Lamp2a, RNA sequence analysis was conducted using rat Schwann cells overexpressing Lamp2a. The nine hub genes (Snrpf, Polr1d, Snip1, Aqr, Polr2h, Ssbp1, Mterf3, Adcy6, and Sbds) were identified using the CytoHubba plugin of Cytoscape. Functional analysis revealed that Lamp2a overexpression affected the transcription levels of genes associated with mitotic spindle organization and mRNA splicing via the spliceosome. In addition, Polr1d and Snrpf1 were downregulated throughout postnatal development but elevated following sciatic nerve injury, according to a bioinformatics study. CMA may be an integral pathway in sciatic nerve injury via mRNA splicing.

Identifiants

pubmed: 38935077
doi: 10.1097/WNR.0000000000002066
pii: 00001756-990000000-00257
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Références

Waller A. Experiments on the section of the glosso-pharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres. Edinb Med Surg J 1851; 76:369–376.
Stoll G, Jander S, Myers RR. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller’s observations to neuroinflammation. J Peripher Nerv Syst 2002; 7:13–27.
Arthur-Farraj PJ, Morgan CC, Adamowicz M, Gomez-Sanchez JA, Fazal SV, Beucher A, et al. Changes in the coding and non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury. Cell Rep 2017; 20:2719–2734.
Kaushik S, Cuervo AM. Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol 2012; 22:407–417.
Orenstein SJ, Cuervo AM. Chaperone-mediated autophagy: molecular mechanisms and physiological relevance. Semin Cell Dev Biol 2010; 21:719–726.
Cuervo AM, Dice JF. A receptor for the selective uptake and degradation of proteins by lysosomes. Science 1996; 273:501–503.
Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM. Identification of regulators of chaperone-mediated autophagy. Mol Cell 2010; 39:535–547.
Jang SY, Shin YK, Park SY, Park JY, Rha SH, Kim JK, et al. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve. PLoS One 2015; 10:e0116624.
Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M, Griffith M, et al. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves. J Cell Biol 2015; 210:153–168.
Huang HC, Chen L, Zhang HX, Li SF, Liu P, Zhao TY, et al. Autophagy promotes peripheral nerve regeneration and motor recovery following sciatic nerve crush injury in rats. J Mol Neurosci 2016; 58:416–423.
Thumm M, Simons M. Myelinophagy: Schwann cells dine in. J Cell Biol 2015; 210:9–10.
Adilakshmi T, Sudol I, Tapinos N. Combinatorial action of miRNAs regulates transcriptional and post-transcriptional gene silencing following in vivo PNS injury. PLoS One 2012; 7:e39674.
Brosius Lutz A, Lucas TA, Carson GA, Caneda C, Zhou L, Barres BA, et al. An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury. J Neuroinflammation 2022; 19:105.
Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 2000; 28:27–30.
Gerber D, Pereira JA, Gerber J, Tan G, Dimitrieva S, Yanguez E, et al. Transcriptional profiling of mouse peripheral nerves to the single-cell level to build a sciatic nerve ATlas (SNAT). Elife 2021; 10.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47(D1):D607–D613.
Qi L, Zhang XD. Role of chaperone-mediated autophagy in degrading Huntington’s disease-associated huntingtin protein. Acta Biochim Biophys Sin (Shanghai) 2014; 46:83–91.
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014; 8 (Suppl 4):S11.
Austin PJ, Berglund AM, Siu S, Fiore NT, Gerke-Duncan MB, Ollerenshaw SL, et al. Evidence for a distinct neuro-immune signature in rats that develop behavioural disability after nerve injury. J Neuroinflammation 2015; 12:96.
Issa AR, Sun J, Petitgas C, Mesquita A, Dulac A, Robin M, et al. The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain. Autophagy 2018; 14:1898–1910.
Cuervo AM, Dice JF. Regulation of lamp2a levels in the lysosomal membrane. Traffic 2000; 1:570–583.
Agarraberes FA, Terlecky SR, Dice JF. An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol 1997; 137:825–834.
Xilouri M, Brekk OR, Landeck N, Pitychoutis PM, Papasilekas T, Papadopoulou-Daifoti Z, et al. Boosting chaperone-mediated autophagy in vivo mitigates alpha-synuclein-induced neurodegeneration. Brain 2013; 136:2130–2146.
Zhang C, Cuervo AM. Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 2008; 14:959–965.
Zhao Y, Zhao W, Han Y. Inhibition of mTORC2 improves brain injury in epileptic rats by promoting chaperone-mediated autophagy. Epilepsy Res 2023; 193:107161.
Li Y, Fan Z, Jia Q, Ma H, Wu Y, Guo X, et al. Chaperone-mediated autophagy (CMA) alleviates cognitive impairment by reducing neuronal death in sepsis-associated encephalopathy (SAE). Exp Neurol 2023; 365:114417.
Liao S, Chen Y, Luo Y, Zhang M, Min J. The phenotypic changes of Schwann cells promote the functional repair of nerve injury. Neuropeptides 2024; 106:102438.
Svaren J, Meijer D. The molecular machinery of myelin gene transcription in Schwann cells. Glia 2008; 56:1541–1551.
Ghislain J, Charnay P. Control of myelination in Schwann cells: a Krox20 cis-regulatory element integrates Oct6, Brn2 and Sox10 activities. EMBO Rep 2006; 7:52–58.
Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, et al. Krox-20 controls myelination in the peripheral nervous system. Nature 1994; 371:796–799.
Boerboom A, Dion V, Chariot A, Franzen R. Molecular mechanisms involved in Schwann cell plasticity. Front Mol Neurosci 2017; 10:38.
Agthong S, Kaewsema A, Tanomsridejchai N, Chentanez V. Activation of MAPK ERK in peripheral nerve after injury. BMC Neurosci 2006; 7:45.
Agthong S, Koonam J, Kaewsema A, Chentanez V. Inhibition of MAPK ERK impairs axonal regeneration without an effect on neuronal loss after nerve injury. Neurol Res 2009; 31:1068–1074.
Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G. Gemin3: a novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. J Cell Biol 1999; 147:1181–1194.
Noack Watt KE, Achilleos A, Neben CL, Merrill AE, Trainor PA. The roles of RNA polymerase I and III subunits Polr1c and Polr1d in craniofacial development and in Zebrafish models of Treacher Collins syndrome. PLoS Genet 2016; 12:e1006187.
Dauwerse JG, Dixon J, Seland S, Ruivenkamp CA, van Haeringen A, Hoefsloot LH, et al. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet 2011; 43:20–22.
Fury MG, Zhang W, Christodoulopoulos I, Zieve GW. Multiple protein: protein interactions between the snRNP common core proteins. Exp Cell Res 1997; 237:63–69.
Malmegrim de Farias KC, Saelens X, Pruijn GJ, Vandenabeele P, van Venrooij WJ. Caspase-mediated cleavage of the U snRNP-associated Sm-F protein during apoptosis. Cell Death Differ 2003; 10:570–579.
Liu J, Gu L, Zhang D, Li W. Determining the prognostic value of spliceosome-related genes in hepatocellular carcinoma patients. Front Mol Biosci 2022; 9:759792.

Auteurs

Eun Jung Sohn (EJ)

Department of Biotechnology, Inje University, Kimhae-si.
Department of Molecular Neuroscience, College of Medicine, Dong-A University, Busan, Korea.

Kun-Taek Park (KT)

Department of Biotechnology, Inje University, Kimhae-si.

Classifications MeSH