血管周细胞在创伤性脊髓损伤后形成纤维疤痕。
Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury.
机构信息
Department of Neurological Surgery, University of Miami, Miami, FL, USA.
出版信息
J Neurosci. 2013 Aug 21;33(34):13882-7. doi: 10.1523/JNEUROSCI.2524-13.2013.
Abstract
Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1α1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1α1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1α1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation.
摘要
中枢神经系统损伤会导致疤痕组织的形成，这对于封闭损伤部位和抑制轴突再生非常重要。由密集细胞外基质组成的纤维性瘢痕被认为起源于围绕中枢神经系统的脑膜细胞。然而，我们利用转基因小鼠证明，在硬脑膜完整的挫伤性脊髓损伤后，血管周胶原 1α1 细胞是纤维性瘢痕细胞成分的主要来源。通过遗传谱系追踪、光片荧光显微镜和抗原分析，我们确定胶原 1α1 细胞是血管周成纤维细胞，与周细胞不同。我们的结果确定了胶原 1α1 细胞是脊髓损伤后纤维性瘢痕的一个新来源，并将瘢痕形成过程中的焦点从脑膜转移到血管。
相似文献
1
Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury.血管周细胞在创伤性脊髓损伤后形成纤维疤痕。
J Neurosci. 2013 Aug 21;33(34):13882-7. doi: 10.1523/JNEUROSCI.2524-13.2013.
2
Proliferating NG2-Cell-Dependent Angiogenesis and Scar Formation Alter Axon Growth and Functional Recovery After Spinal Cord Injury in Mice.NG2 细胞依赖性血管生成和瘢痕形成促进小鼠脊髓损伤后的轴突生长和功能恢复。
J Neurosci. 2018 Feb 7;38(6):1366-1382. doi: 10.1523/JNEUROSCI.3953-16.2017. Epub 2017 Dec 26.
3
Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys.异质性成纤维细胞有助于小鼠和猴子脊髓损伤后的纤维化瘢痕形成。
Nat Commun. 2024 Jul 27;15(1):6321. doi: 10.1038/s41467-024-50564-x.
4
Distinct origin and region-dependent contribution of stromal fibroblasts to fibrosis following traumatic injury in mice.小鼠创伤后纤维化中基质成纤维细胞的不同起源和区域依赖性贡献。
Nat Neurosci. 2024 Jul;27(7):1285-1298. doi: 10.1038/s41593-024-01678-4. Epub 2024 Jun 7.
5
Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions.周细胞衍生的纤维瘢痕在不同的中枢神经系统病变中是保守存在的。
Nat Commun. 2021 Sep 17;12(1):5501. doi: 10.1038/s41467-021-25585-5.
6
Reactive Fibroblasts in Response to Optic Nerve Crush Injury.反应性成纤维细胞对视神经挤压损伤的反应。
Mol Neurobiol. 2021 Apr;58(4):1392-1403. doi: 10.1007/s12035-020-02199-4. Epub 2020 Nov 12.
7
Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury.胶质瘢痕边界由新增殖的、伸长的星形胶质细胞形成，这些细胞通过 STAT3 依赖的机制相互作用，在脊髓损伤后隔离炎症和纤维细胞。
J Neurosci. 2013 Jul 31;33(31):12870-86. doi: 10.1523/JNEUROSCI.2121-13.2013.
8
Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury.血源性巨噬细胞清除可减少脊髓损伤后的纤维化瘢痕并促进轴突生长。
Neurobiol Dis. 2015 Feb;74:114-25. doi: 10.1016/j.nbd.2014.10.024. Epub 2014 Nov 4.
9
SU16f inhibits fibrotic scar formation and facilitates axon regeneration and locomotor function recovery after spinal cord injury by blocking the PDGFRβ pathway.SU16f 通过阻断 PDGFRβ 通路抑制纤维化瘢痕形成，并促进脊髓损伤后的轴突再生和运动功能恢复。
J Neuroinflammation. 2022 Apr 16;19(1):95. doi: 10.1186/s12974-022-02449-3.
10
A pericyte origin of spinal cord scar tissue.脊髓瘢痕组织的周细胞起源。
Science. 2011 Jul 8;333(6039):238-42. doi: 10.1126/science.1203165.
引用本文的文献
1
Dynamic fibroblast-immune interactions shape recovery after brain injury.动态的成纤维细胞 - 免疫相互作用塑造脑损伤后的恢复过程。
Nature. 2025 Sep 3. doi: 10.1038/s41586-025-09449-2.
2
in vivo Reprogramming of NG2 Glia Improves Bladder Function After Spinal Cord Injury.脊髓损伤后，体内对少突胶质前体细胞进行重编程可改善膀胱功能。
bioRxiv. 2025 Jul 31:2025.07.28.667292. doi: 10.1101/2025.07.28.667292.
3
Meflin/Islr is a marker of fibroblasts that arise in fibrotic regions after spinal cord injury.Meflin/Islr是脊髓损伤后在纤维化区域出现的成纤维细胞的标志物。
Nagoya J Med Sci. 2025 May;87(2):305-319. doi: 10.18999/nagjms.87.2.305.
4
Mechanisms underpinning spontaneous spinal cord regeneration.脊髓自发再生的潜在机制。
Development. 2025 Oct 15;152(20). doi: 10.1242/dev.204790. Epub 2025 Jul 30.
5
Molecular pathology of acute spinal cord injury in middle-aged mice.中年小鼠急性脊髓损伤的分子病理学
J Neuroinflammation. 2025 Jul 13;22(1):181. doi: 10.1186/s12974-025-03494-4.
6
Brain macrophages and pial fibroblasts promote inflammation in a hypomyelination model.脑巨噬细胞和软脑膜成纤维细胞在髓鞘形成不足模型中促进炎症反应。
Acta Neuropathol Commun. 2025 Jul 4;13(1):145. doi: 10.1186/s40478-025-02063-3.
7
"PDGFRα is required for postnatal cerebral perivascular fibroblast development".出生后大脑血管周围成纤维细胞的发育需要血小板衍生生长因子受体α（PDGFRα）
bioRxiv. 2025 Jun 7:2025.06.07.658411. doi: 10.1101/2025.06.07.658411.
8
Molecular pathology of acute spinal cord injury in middle-aged mice.中年小鼠急性脊髓损伤的分子病理学
bioRxiv. 2025 May 14:2025.05.08.652873. doi: 10.1101/2025.05.08.652873.
9
Pericytes in the Pulmonary Microenvironment: Guardians or Adversaries?肺微环境中的周细胞：守护者还是对手？
Lung. 2025 May 31;203(1):65. doi: 10.1007/s00408-025-00820-8.
10
Blueprints for healing: central nervous system regeneration in zebrafish and neonatal mice.愈合蓝图：斑马鱼和新生小鼠的中枢神经系统再生
BMC Biol. 2025 Apr 30;23(1):115. doi: 10.1186/s12915-025-02203-0.
本文引用的文献
1
Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.周细胞：发育、生理和病理视角、问题和前景。
Dev Cell. 2011 Aug 16;21(2):193-215. doi: 10.1016/j.devcel.2011.07.001.
2
A pericyte origin of spinal cord scar tissue.脊髓瘢痕组织的周细胞起源。
Science. 2011 Jul 8;333(6039):238-42. doi: 10.1126/science.1203165.
3
Age-dependent fate and lineage restriction of single NG2 cells.NG2 细胞的年龄依赖性命运和谱系限制。
Development. 2011 Feb;138(4):745-53. doi: 10.1242/dev.047951.
4
Combined genetic attenuation of myelin and semaphorin-mediated growth inhibition is insufficient to promote serotonergic axon regeneration.联合遗传减弱髓鞘和神经递质介导的生长抑制不足以促进血清素能轴突再生。
J Neurosci. 2010 Aug 11;30(32):10899-904. doi: 10.1523/JNEUROSCI.2269-10.2010.
5
Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.评估 Nogo、MAG 和 OMgp 缺失小鼠的脊髓轴突再生和发芽。
Neuron. 2010 Jun 10;66(5):663-70. doi: 10.1016/j.neuron.2010.05.002.
6
3D-reconstruction of blood vessels by ultramicroscopy.通过超微镜对血管进行三维重建。
Organogenesis. 2009 Oct;5(4):227-30. doi: 10.4161/org.5.4.10403.
7
Generation of an OMgp allelic series in mice.在小鼠中生成OMgp等位基因系列。
Genesis. 2009 Nov;47(11):751-6. doi: 10.1002/dvg.20557.
8
CNS pericytes: concepts, misconceptions, and a way out.中枢神经系统周细胞：概念、误解与出路。
Glia. 2010 Jan 1;58(1):1-10. doi: 10.1002/glia.20898.
9
Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney.周细胞和血管周围成纤维细胞是肾梗阻性纤维化中产生胶原蛋白细胞的主要来源。
Am J Pathol. 2008 Dec;173(6):1617-27. doi: 10.2353/ajpath.2008.080433. Epub 2008 Nov 13.
10
Robust axonal growth and a blunted macrophage response are associated with impaired functional recovery after spinal cord injury in the MRL/MpJ mouse.在MRL/MpJ小鼠中，强劲的轴突生长和减弱的巨噬细胞反应与脊髓损伤后功能恢复受损有关。
Neuroscience. 2008 Oct 15;156(3):498-514. doi: 10.1016/j.neuroscience.2008.08.013. Epub 2008 Aug 19.
Zotero 插件