HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration

Dong, Yingying; Gu, Yun; Huan, Youjuan; Wang, Yingjie; Liu, Yan; Ding, Fei; Gu, Xiaosong; Wang, Yongjun

doi:10.1074/jbc.m113.463810

Cited by 38 publications

(47 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sidney Simpson, JR., and Lorenzo Alibardi (Simpson, 1964;Simpson and Cox, 1967;Alibardi and Meyer-Rochow, 1989). Work with lizard tail regeneration has since grown steadily, and recently a handful of groups began focusing on this research area (McLean and Vickaryous, 2011;Wang et al, 2011;Delorme et al, 2012;Fisher et al, 2012;Dong et al, 2013;Eckalbar et al, 2013;Hutchins et al, 2014). Our study described here presents several first-time observations that should enhance our understanding of this unique biological phenomenon.…”

Section: Discussionmentioning

confidence: 68%

Lizard tail regeneration: regulation of two distinct cartilage regions by Indian hedgehog

Lozito

Tuan

2015

Developmental Biology

View full text Add to dashboard Cite

Lizards capable of caudal autotomy exhibit the remarkable ability to "drop" and then regenerate their tails. However, the regenerated lizard tail (RLT) is known as an "imperfect replicate" due to several key anatomical differences compared to the original tail. Most striking of these "imperfections" concerns the skeleton; instead of the vertebrae of the original tail, the skeleton of the RLT takes the form of an unsegmented cartilage tube (CT). Here we have performed the first detailed staging of skeletal development of the RLT CT, identifying two distinct mineralization events. CTs isolated from RLTs of various ages were analyzed by micro-computed tomography to characterize mineralization, and to correlate skeletal development with expression of endochondral ossification markers evaluated by histology and immunohistochemistry. During early tail regeneration, shortly after CT formation, the extreme proximal CT in direct contact with the most terminal vertebra of the original tail develops a growth plate-like region that undergoes endochondral ossification. Proximal CT chondrocytes enlarge, express hypertrophic markers, including Indian hedgehog (Ihh), apoptose, and are replaced by bone. During later stages of tail regeneration, the distal CT mineralizes without endochondral ossification. The sub-perichondrium of the distal CT expresses Ihh, and the perichondrium directly calcifies without cartilage growth plate formation. The calcified CT perichondrium also contains a population of stem/progenitor cells that forms new cartilage in response to TGF-β stimulation. Treatment with the Ihh inhibitor cyclopamine inhibited both proximal CT ossification and distal CT calcification. Thus, while the two mineralization events are spatially, temporally, and mechanistically very different, they both involve Ihh. Taken together, these results suggest that Ihh regulates CT mineralization during two distinct stages of lizard tail regeneration.

show abstract

Section: Discussionmentioning

confidence: 68%

Lizard tail regeneration: regulation of two distinct cartilage regions by Indian hedgehog

Lozito

Tuan

2015

Developmental Biology

View full text Add to dashboard Cite

show abstract

“…In particular, HMGB1 was shown to contribute to spinal cord regeneration in animal models where spontaneous regeneration occurs (41,42). Our data, showing that HMGB1 released from damaged OLs provides protective effects on OLs under ischemic stress, add a cellular trophic function to the list of the noninflammatory biological effects of HMGB1.…”

Section: Discussionmentioning

confidence: 78%

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Maintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress. HMGB1 rapidly accumulated in the culture medium of OLs exposed to oxygen-glucose deprivation (OGD). This conditioned medium exhibited a protective activity against ischemic OL death that was completely abolished by immunodepletion of HMGB1. Knockdown of HMGB1 or application of glycyrrhizin, a specific HMGB1 inhibitor, aggravated OGD-induced OL death, and recombinant HMGB1 application reduced the extent of OL death in a TLR2-dependent manner. We confirmed that cytosolic translocation of HMGB1 and activation of TLR2-mediated signaling pathways occurred in a focal white matter stroke model induced by endothelin-1 injection. Animals with glycyrrhizin coinjection showed an expansion of the demyelinating lesion in a TLR2-dependent manner, accompanied by aggravation of sensorimotor behavioral deficits. These results indicate that HMGB1/ TLR2 activates an autocrine trophic signaling pathways in OLs and myelin to maintain structural and functional integrity of the white matter under ischemic conditions. white matter stroke | oligodendrocyte | toll-like receptor 2 | HMGB1 | myelination W hite matter in the vertebrate brain is characterized by the presence of myelinated axonal fibers and glial cells, predominantly myelin-producing oligodendrocytes (OLs) (1). The myelin sheath enables rapid communication of neural signals at a millisecond timescale between different parts of the cerebral cortex or different regions of the CNS (2). Therefore, maintaining the integrity of white matter in health and disease, especially of OLs and the myelin sheath, is critical to the performance of a variety of brain functions. Furthermore, recent studies have shown that myelination and OL generation in adulthood are actively regulated in response to neural activities (3, 4), highlighting the potential contribution of white matter plasticity to learning and higher cognitive functions.Ischemic stroke that occurs in the white matter often results in degeneration of OLs and demyelination (5, 6). Consequently, patients with white matter stroke suffer from a wide range of neurological dysfunctions. For example, focal ischemic stroke in the internal capsule may result in severe hemiparesis (7). Furthermore, both cognitive deficits and gait disturbance are hallmarks of Binswanger's subcortical vascular dementia that is the most severe form of white matter stroke (8). How ischemia leads to OL degeneration and demyelination is poorly understood. We previously reported that toll-like receptor 2 (TLR2) expressed in OLs plays a protect...

show abstract

“…Interestingly, HMGB1 has also been found beneficial in promoting CNS repair in non-mammalian organisms. For example, a gecko paralog of HMGB1 was shown to signal via RAGE to oligodendrocytes to coordinate myelination after CNS injury (Dong et al, 2013) and to neurons to promote neurite outgrowth (Saleh et al, 2013). HMGB1 also contributes to axonal regeneration and recovery after spinal cord transection in a zebrafish model (Fang et al, 2014).…”

Section: High-mobility Group Protein B1mentioning

confidence: 99%

“…HMGB1 also contributes to axonal regeneration and recovery after spinal cord transection in a zebrafish model (Fang et al, 2014). The opposing roles of HMGB1 described in different organisms may be less puzzling, however given a recent study demonstrating that paralogs of gecko HMGB1 have other functions, unrelated to inflammation, that directly support remyelination and CNS regeneration in these animals (Dong et al, 2013). …”

Section: High-mobility Group Protein B1mentioning

confidence: 99%

Dealing with Danger in the CNS: The Response of the Immune System to Injury

Gadani

Walsh

Lukens

et al. 2015

Neuron

266

260

View full text Add to dashboard Cite

Fighting pathogens and maintaining tissue homeostasis are prerequisites for survival. Both of these functions are upheld by the immune system, though the latter is often overlooked in the context of the CNS. The mere presence of immune cells in the CNS was long considered a hallmark of pathology, but this view has been recently challenged by studies demonstrating that immunological signaling can confer pivotal neuroprotective effects on the injured CNS. In this review we describe the temporal sequence of immunological events that follow CNS injury. Beginning with immediate changes at the injury site including death of neural cells and release of damage-associated molecular patterns (DAMPs), and progressing through innate and adaptive immune responses, we describe the cascade of inflammatory mediators and the implications of their post-injury effects. We conclude by proposing a revised interpretation of immune privilege in the brain, which takes beneficial neuro-immune communications into account.

show abstract

HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration

Cited by 38 publications

References 95 publications

Lizard tail regeneration: regulation of two distinct cartilage regions by Indian hedgehog

Lizard tail regeneration: regulation of two distinct cartilage regions by Indian hedgehog

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Dealing with Danger in the CNS: The Response of the Immune System to Injury

Contact Info

Product

Resources

About