Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.

Crush injury or axotomy of peripheral nerves results in the rapid production of the inflammatory cytokines, which were confirmed in various models, to some extent, to be noxious to the myelin sheath or Schwann cells (SCs). TNF-α is one of the primary initiators of the inflammatory cascade and exerts...

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Autores principales: Yongjun Wang, Xin Tang, Bin Yu, Yun Gu, Ying Yuan, Dengbing Yao, Fei Ding, Xiaosong Gu
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:77c19a124173440db67fb11f3c4139582021-11-18T07:05:26ZGene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.1932-620310.1371/journal.pone.0043436https://doaj.org/article/77c19a124173440db67fb11f3c4139582012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028454/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Crush injury or axotomy of peripheral nerves results in the rapid production of the inflammatory cytokines, which were confirmed in various models, to some extent, to be noxious to the myelin sheath or Schwann cells (SCs). TNF-α is one of the primary initiators of the inflammatory cascade and exerts pleiotropic functions in the physiological conditions by binding to its receptors, type I (TNFRI) and type II (TNFRII). The pathway molecules TNFRI, Birc2 and Birc3 play key roles during the activation of the signaling. Injured peripheral nerves, preventing them from TNF-α-mediated destruction and proceeding to successful regeneration, might initiate an anti-apoptotic mechanism. To identity the exact functions of TNFRI, Birc2 and Birc3, as well as its involved pathways in the cellular events, we inferred a dynamic gene regulatory network from short time-series measurements of the proximal nerve segment cDNA microarray following rat sciatic nerve transection. TNFRI family member Tnfrsf1a, Birc2 and Birc3 were mined out integrating as master regulators to mediate inflammatory responses. Experiments revealed that Tnfrsf1a, Birc2 and Birc3 proteins colocalized with S100 in the rat peripheral nerve tissues, and the expression levels increased with the time extension. Knockdown of the proteins induced the apoptotic formation of primary cultured SCs by upregulation of caspase 3 and caspase 6. Our systematic analysis indicated that Tnfrsf1a, Birc2 and Birc3 of SCs, not originally regarded as XIAP, were mainly responsible for the inflammation-mediated anti-apoptosis of peripheral nerves. Birc2 and Birc3 might be the most potential targets for anti-apoptotic protection mediated by inflammatory cytokines.Yongjun WangXin TangBin YuYun GuYing YuanDengbing YaoFei DingXiaosong GuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e43436 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yongjun Wang
Xin Tang
Bin Yu
Yun Gu
Ying Yuan
Dengbing Yao
Fei Ding
Xiaosong Gu
Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.
description Crush injury or axotomy of peripheral nerves results in the rapid production of the inflammatory cytokines, which were confirmed in various models, to some extent, to be noxious to the myelin sheath or Schwann cells (SCs). TNF-α is one of the primary initiators of the inflammatory cascade and exerts pleiotropic functions in the physiological conditions by binding to its receptors, type I (TNFRI) and type II (TNFRII). The pathway molecules TNFRI, Birc2 and Birc3 play key roles during the activation of the signaling. Injured peripheral nerves, preventing them from TNF-α-mediated destruction and proceeding to successful regeneration, might initiate an anti-apoptotic mechanism. To identity the exact functions of TNFRI, Birc2 and Birc3, as well as its involved pathways in the cellular events, we inferred a dynamic gene regulatory network from short time-series measurements of the proximal nerve segment cDNA microarray following rat sciatic nerve transection. TNFRI family member Tnfrsf1a, Birc2 and Birc3 were mined out integrating as master regulators to mediate inflammatory responses. Experiments revealed that Tnfrsf1a, Birc2 and Birc3 proteins colocalized with S100 in the rat peripheral nerve tissues, and the expression levels increased with the time extension. Knockdown of the proteins induced the apoptotic formation of primary cultured SCs by upregulation of caspase 3 and caspase 6. Our systematic analysis indicated that Tnfrsf1a, Birc2 and Birc3 of SCs, not originally regarded as XIAP, were mainly responsible for the inflammation-mediated anti-apoptosis of peripheral nerves. Birc2 and Birc3 might be the most potential targets for anti-apoptotic protection mediated by inflammatory cytokines.
format article
author Yongjun Wang
Xin Tang
Bin Yu
Yun Gu
Ying Yuan
Dengbing Yao
Fei Ding
Xiaosong Gu
author_facet Yongjun Wang
Xin Tang
Bin Yu
Yun Gu
Ying Yuan
Dengbing Yao
Fei Ding
Xiaosong Gu
author_sort Yongjun Wang
title Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.
title_short Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.
title_full Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.
title_fullStr Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.
title_full_unstemmed Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.
title_sort gene network revealed involvements of birc2, birc3 and tnfrsf1a in anti-apoptosis of injured peripheral nerves.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/77c19a124173440db67fb11f3c413958
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