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Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms.
Exp Neurol. 2001 Nov; 172(1):182-8.EN

Abstract

Transforming growth factor-alpha (TGF-alpha), previously identified as a major member of the epidermal growth factor (EGF) family of growth factors, plays a role in proliferation, differentiation, and survival of neuronal and glial precursors and is implicated in development of the nervous system. However, its roles in nerve injury-induced responses remain obscure. The current study examined roles of endogenous TGF-alpha in peripheral nerve regeneration using sciatic nerve injury models with TGF-alpha knockout mice. Three weeks after a sciatic nerve crush, no significant differences were found between TGF-alpha wild-type and mutant mice in the number of retrogradely labeled L5 dorsal root ganglion (DRG) sensory neurons and L5 spinal cord motor neurons and in the morphology of myelinated regenerating nerve fibers, indicating that TGF-alpha is not essential for sensory and motor nerve regeneration. To assess a possible functional redundancy among TGF-alpha-related ligands in response to a nerve injury, mRNA expression of the EGF family was analyzed by RT-PCR in L4/L5 DRG pools and distal degenerating sciatic nerve segments after sciatic nerve ligation. Prior to and 1 day after ligation, there was a higher level of EGF-R mRNA in DRGs and in nerve in TGF-alpha null mice compared to wild types, and there was an induction of ligand amphiregulin mRNA in DRGs in mutant mice in place of the TGF-alpha upregulation present in wild types. These results indicate that TGF-alpha gene knockout does not affect peripheral nerve regeneration, probably due to a functional redundancy within the EGF family through a compensatory expression mechanism at both the receptor and ligand levels in TGF-alpha knockout mice.

Authors+Show Affiliations

Department of Human Physiology, Flinders University of South Australia, Adelaide 5001, Australia. cory.xian@adelaide.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11681850

Citation

Xian, C J., et al. "Lack of Effects of Transforming Growth Factor-alpha Gene Knockout On Peripheral Nerve Regeneration May Result From Compensatory Mechanisms." Experimental Neurology, vol. 172, no. 1, 2001, pp. 182-8.
Xian CJ, Li L, Deng YS, et al. Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms. Exp Neurol. 2001;172(1):182-8.
Xian, C. J., Li, L., Deng, Y. S., Zhao, S. P., & Zhou, X. F. (2001). Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms. Experimental Neurology, 172(1), 182-8.
Xian CJ, et al. Lack of Effects of Transforming Growth Factor-alpha Gene Knockout On Peripheral Nerve Regeneration May Result From Compensatory Mechanisms. Exp Neurol. 2001;172(1):182-8. PubMed PMID: 11681850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms. AU - Xian,C J, AU - Li,L, AU - Deng,Y S, AU - Zhao,S P, AU - Zhou,X F, PY - 2001/10/30/pubmed PY - 2002/1/5/medline PY - 2001/10/30/entrez SP - 182 EP - 8 JF - Experimental neurology JO - Exp Neurol VL - 172 IS - 1 N2 - Transforming growth factor-alpha (TGF-alpha), previously identified as a major member of the epidermal growth factor (EGF) family of growth factors, plays a role in proliferation, differentiation, and survival of neuronal and glial precursors and is implicated in development of the nervous system. However, its roles in nerve injury-induced responses remain obscure. The current study examined roles of endogenous TGF-alpha in peripheral nerve regeneration using sciatic nerve injury models with TGF-alpha knockout mice. Three weeks after a sciatic nerve crush, no significant differences were found between TGF-alpha wild-type and mutant mice in the number of retrogradely labeled L5 dorsal root ganglion (DRG) sensory neurons and L5 spinal cord motor neurons and in the morphology of myelinated regenerating nerve fibers, indicating that TGF-alpha is not essential for sensory and motor nerve regeneration. To assess a possible functional redundancy among TGF-alpha-related ligands in response to a nerve injury, mRNA expression of the EGF family was analyzed by RT-PCR in L4/L5 DRG pools and distal degenerating sciatic nerve segments after sciatic nerve ligation. Prior to and 1 day after ligation, there was a higher level of EGF-R mRNA in DRGs and in nerve in TGF-alpha null mice compared to wild types, and there was an induction of ligand amphiregulin mRNA in DRGs in mutant mice in place of the TGF-alpha upregulation present in wild types. These results indicate that TGF-alpha gene knockout does not affect peripheral nerve regeneration, probably due to a functional redundancy within the EGF family through a compensatory expression mechanism at both the receptor and ligand levels in TGF-alpha knockout mice. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/11681850/Lack_of_effects_of_transforming_growth_factor_alpha_gene_knockout_on_peripheral_nerve_regeneration_may_result_from_compensatory_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(01)97771-4 DB - PRIME DP - Unbound Medicine ER -