TGF-β Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro

Song, Gongyu; Yang, Runyu; Zhang, Qian; Chen, Long; Huang, Dujuan; Zeng, Junwei; Yang, Changpei; Zhang, Tao

doi:10.1007/s12031-019-01361-5

Cited by 37 publications

(26 citation statements)

References 36 publications

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“…In vitro, M1 macrophages are essential inducers of astrocytic activation (Haan et al, 2015). On the other hand, M2 macrophages secrete TGF-β to induce glial scar formation in vitro (Song et al, 2019). M2 macrophages may also enhance the polarization of reactive astrocytes after SCI (Sonn et al, 2019).…”

Section: Macrophagesmentioning

confidence: 99%

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Yang

Dai

Chen

et al. 2020

Front. Cell. Neurosci.

162

161

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Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

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Section: Macrophagesmentioning

confidence: 99%

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Yang

Dai

Chen

et al. 2020

Front. Cell. Neurosci.

162

161

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“…During development, Transforming growth factor beta helps regulate neuronal survival, neurogenesis, synaptogenesis, and gliogenesis (Figure 1) (88,89). Astroglia expression of TGF-β mediates synaptic refinement as well as glial scar formation (90,91). Abnormal TGF-β hyperactivation has been detected in neurodegenerative disease and traumatic injury patients, and astrocytes and microglia are the predominate source (92)(93)(94)(95).…”

Section: Signaling Cascades Associated With Astrocytes In Admentioning

confidence: 99%

The Many Faces of Astrocytes in Alzheimer's Disease

Monterey

Wei

et al. 2021

Front. Neurol.

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Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common cause of dementia in an aging population. The majority of research effort has focused on the role of neurons in neurodegeneration and current therapies have limited ability to slow disease progression. Recently more attention has been given to the role of astrocytes in the process of neurodegeneration. Specifically, reactive astrocytes have both advantageous and adverse effects during neurodegeneration. The ability to isolate and depict astrocyte phenotype has been challenging. However, with the recent development of single-cell sequencing technologies researchers are provided with the resource to delineate specific biomarkers associated with reactive astrocytes in AD. In this review, we will focus on the role of astrocytes in normal conditions and the pathological development of AD. We will further review recent developments in the understanding of astrocyte heterogeneity and associated biomarkers. A better understanding of astrocyte contributions and phenotypic changes in AD can ultimately lead to more effective therapeutic targets.

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“…Reactive astrocytes that produce ECM components contribute a pivotal cellular component of glial scars involved in the inhibition of axonal regeneration (Fitch and Silver 2008;Vogelaar et al 2015). TGFβ1 is an inducer of glial scar formation both in vivo and in vitro (Howe et al 2019;Song et al 2019). Thus, reactive glia in lesion situations reacts differently to the TGFβ1 stimulus compared to NSPCs that represent actively cycling cells involved in tissue development and remodeling.…”

Section: Discussionmentioning

confidence: 99%

The expression of tenascin-C in neural stem/progenitor cells is stimulated by the growth factors EGF and FGF-2, but not by TGFβ1

2021

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Neural stem/progenitor cells (NSPCs) rely on internal and external cues determining their lineage decisions during brain development. The progenitor cells of the embryonic mammalian forebrain reside in the ventricular and subventricular zones of the lateral ventricles, where they proliferate, generate neurons and glial cells, and respond to external cues like growth factors. The extracellular matrix (ECM) surrounds NSPCs and influences the cell fate by providing mechanical scaffold, trophic support, and instructive signals. The ECM molecule tenascin-C (Tnc) is expressed in the proliferative zones of the developing forebrain and involved in the proliferation and maturation of NSPCs. Here, we analyzed the regulation of the Tnc gene expression by NSPCs cultivated under the influence of different growth factors. We observed that the epidermal growth factor (EGF) and the fibroblast growth factor (FGF)-2 strongly increased the expression of Tnc, whereas the transforming growth factor (TGF)β 1 had no effect on Tnc gene expression, in contrast to previous findings in cell cultures of neural and non-neural origin. The stimulation of the Tnc gene expression induced by EGF or FGF-2 was reversible and seen in constantly treated as well as short term stimulated NSPC cultures. The activation depended on the presence of the respective receptors, which was slightly different in cortical and striatal NSPC cultures. Our results confirm the influence of extracellular stimuli regulating the expression of factors that form a niche for NSPCs during embryonic forebrain development.

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TGF-β Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro

Cited by 37 publications

References 36 publications

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

The Many Faces of Astrocytes in Alzheimer's Disease

The expression of tenascin-C in neural stem/progenitor cells is stimulated by the growth factors EGF and FGF-2, but not by TGFβ1

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