Oncomodulin links inflammation to optic nerve regeneration

Yin, Yuqin; Cui, Qing; Gilbert, Hui-ya; Yang, Yang; Yang, Zhiyong; Berlinicke, Cynthia; Li, Zhiwei; Zaverucha-do-Valle, Camila; He, Hongqing; Petkova, Victoria; Zack, Donald J.; Benowitz, Larry I.

doi:10.1073/pnas.0907085106

Cited by 179 publications

(198 citation statements)

References 32 publications

Supporting

Mentioning

188

Contrasting

Order By: Relevance

“…Although this is the first time OCM and OCM receptors are put in evidence in injured pancreas, our results are consistent with previous report on OCM that show that OCM produced following tissues injury [4,11,13].…”

Section: Discussionsupporting

confidence: 83%

“…Macrophages derived factors have been shown to play and influence the mechanism leading to injury healing and tissues regeneration. Recently, it has been shown that factors secreted by tissue-infiltrated macrophages such as oncomodulin (OCM), a small, ~12 kDa calcium-binding protein in the parvalbumin family had a regenerative and growth promoting effect on retinal ganglion cell axon [2][3][4]. Furthermore, the regeneration of beta cells after injury has lead to the concept that factors derived from injury related immune response (or inflammation) might be involved beta cells progeny differentiation and maturation [5].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oncomodulin and macrophages derived factors in pancreas injury and development paradigms

Siawaya¹,

Capito²,

Scharfmann³

2013

MRI

View full text Add to dashboard Cite

Prior studies in the optic nerve injury paradigm showed conflicting data regarding production and significance of the Ca 2+ -binding protein oncomodulin (OCM). Some have shown its potent axon-regenerative or-growth attribute, where other showed little to no effect. We show here that pancreas inflammation lead to macrophages infiltration that produce OCM and inflamed tissues that express OCM receptors in vivo. In culture OCM has a cytostatic effect on embryonic pancreas explants. Secretory products of zymosanactivated macrophages are cytotoxic and factors derived from non-activated macrophages seem to promote pancreas development. It is our view that OCM is involved in protective injury response that allows through metabolism slowing sub-lethally injured cells to undergo recovery.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Oncomodulin and macrophages derived factors in pancreas injury and development paradigms

Siawaya¹,

Capito²,

Scharfmann³

2013

MRI

View full text Add to dashboard Cite

show abstract

“…The growth state of RGCs can be enhanced by intraocular injection of inflammatory agents such as the Toll-like receptor 2 agonist Zymosan. 35,36 In our study, we observed that the injection of Zymosan at the time of the injury increased the number of regenerating axons by B3-fold in all the groups compared with untreated mice. The enhancement of growing axons was higher in the optic nerves of Cnp-Cre þ / À xRtn4 flox/flox mice than in WT, CnpCre þ / À or Rtn4 flox/flox animals (Figures 2c and d).…”

Section: Resultsmentioning

confidence: 49%

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

et al. 2014

View full text Add to dashboard Cite

Nogo-A is a well-known myelin-enriched inhibitory protein for axonal growth and regeneration in the central nervous system (CNS). Besides oligodendrocytes, our previous data revealed that Nogo-A is also expressed in subpopulations of neurons including retinal ganglion cells, in which it can have a positive role in the neuronal growth response after injury, through an unclear mechanism. In the present study, we analyzed the opposite roles of glial versus neuronal Nogo-A in the injured visual system. To this aim, we created oligodendrocyte (Cnp-Cre þ / À xRtn4/Nogo-A flox/flox ) and neuron-specific (Thy1-Cre tg þ xRtn4 flox/flox ) conditional Nogo-A knock-out (KO) mouse lines. Following complete intraorbital optic nerve crush, both spontaneous and inflammation-mediated axonal outgrowth was increased in the optic nerves of the glia-specific Nogo-A KO mice. In contrast, neuron-specific deletion of Nogo-A in a KO mouse line or after acute gene recombination in retinal ganglion cells mediated by adeno-associated virus serotype 2.Cre virus injection in Rtn4 flox/flox animals decreased axon sprouting in the injured optic nerve. These results therefore show that selective ablation of Nogo-A in oligodendrocytes and myelin in the optic nerve is more effective at enhancing regrowth of injured axons than what has previously been observed in conventional, complete Nogo-A KO mice. Our data also suggest that neuronal Nogo-A in retinal ganglion cells could participate in enhancing axonal sprouting, possibly by cis-interaction with Nogo receptors at the cell membrane that may counteract trans-Nogo-A signaling. We propose that inactivating Nogo-A in glia while preserving neuronal Nogo-A expression may be a successful strategy to promote axonal regeneration in the CNS.

show abstract

“…When injected into brain or spinal cord, zymosan elicits macrophage-mediated killing of neurons while also creating a microenvironment that supports axon regeneration (Fitch et al, 1999;Yin et al, 2003Yin et al, , 2006Yin et al, , 2009Okada et al, 2005;Steinmetz et al, 2005;Benowitz and Popovich, 2011). In this manuscript, new data show that the neurotoxic effects of zymosan-activated macrophages (ZAMs) are due to CLR activation.…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptors and Dectin-1, a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages

Gensel

Wang

Guan

et al. 2015

Journal of Neuroscience

View full text Add to dashboard Cite

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid macrophage reaction; however, only dectin-1 activation causes macrophage-mediated demyelination and axonal injury. Coactivating TLR2 reduced the injurious effects of dectin-1 activation. When injected into traumatically injured spinal cord, TLR2 agonists enhance the endogenous macrophage reaction while conferring neuroprotection. Indeed, dieback of axons was reduced, leading to smaller lesion volumes at the peak of the macrophage response. Moreover, the density of NG2ϩ cells expressing vimentin increased in and near lesions that were enriched with TLR2-activated macrophages. In dectin-1-null mutant (knock-out) mice, dieback of corticospinal tract axons also is reduced after SCI. Collectively, these data support the hypothesis that the ability of macrophages to create an axon growth-permissive microenvironment or cause neurotoxicity is receptor dependent and it may be possible to exploit this functional dichotomy to enhance CNS repair.

show abstract

Oncomodulin links inflammation to optic nerve regeneration

Cited by 179 publications

References 32 publications

Oncomodulin and macrophages derived factors in pancreas injury and development paradigms

Oncomodulin and macrophages derived factors in pancreas injury and development paradigms

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

Toll-Like Receptors and Dectin-1, a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages

Contact Info

Product

Resources

About