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Nidogen plays a role in the regenerative axon growth of adult sensory neurons through Schwann cells.

Lee HK, Seo IA, Suh DJ, Park HT - J. Korean Med. Sci. (2009)

Bottom Line: Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells.Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent.Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Dong-A University, Busan, Korea.

ABSTRACT
We previously reported that nidogen is an extracellular matrix protein regulating Schwann cell proliferation and migration. Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells. Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent. Continuous infusion of recombinant ectodomain of tumor endothelial marker 7, which specifically blocks nidogen function in Schwann cells, suppressed regenerative neurite growth in a sciatic nerve axotomy model. Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.

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In vivo effect of nidogen inhibition on peripheral nerve regeneration. After sciatic nerve axotomy, AP or eTEM7-AP was infused using an Alzet mini-pump for 2 weeks and then the regenerative axons were stained with an anti-Tuj1 antibody. (A) The axonal morphology is high dystrophic in the eTEM7-treated group compared to the Fc-treated group. Scale bar; 100 µm. (B). The diameter of neurites in eTEM7-AP-treated group was thinner than that of AP controls. *P<0.05. (C). The mean lengths of regenerating neurites from AP and eTEMP7-AP-treated group showed no difference.
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Figure 3: In vivo effect of nidogen inhibition on peripheral nerve regeneration. After sciatic nerve axotomy, AP or eTEM7-AP was infused using an Alzet mini-pump for 2 weeks and then the regenerative axons were stained with an anti-Tuj1 antibody. (A) The axonal morphology is high dystrophic in the eTEM7-treated group compared to the Fc-treated group. Scale bar; 100 µm. (B). The diameter of neurites in eTEM7-AP-treated group was thinner than that of AP controls. *P<0.05. (C). The mean lengths of regenerating neurites from AP and eTEMP7-AP-treated group showed no difference.

Mentions: In order to find out an endogenous role of nidogen in peripheral nerve regeneration, we tried to block nidogen using recombinant ectodomain of tumor endothelial marker 7 (eTEM7). We previously showed that TEM7 is a possible transmembrane receptor for nidogen and that eTEM7 can specifically block nidogen function on Schwann cells without affecting laminin or fibronectin functions (19). After sciatic nerve axotomy, we continuously infused recombinant eTEM-AP or AP for 2 weeks using an Alzet mini-osmotic pump. The immunostaining of regenerative axons from proximal stumps of the axotomized sciatic nerves demonstrated that the regenerating axons of the eTEM7-AP-treated group showed signs of abnormal regenerative axon growth, compared to that of AP-treated controls. First, the regenerative axons looked fragile and dystrophic in eTEM7-AP-treated group (Fig. 3A). Second, the diameter of the regenerating axons was thinner in eTEM7-AP-treated group, compared to the AP-control (Fig. 3B). However, the mean length of the regenerating axons in eTEM7-AP-treated group (Fig. 3C) was not significantly shorter than controls. These findings suggest that nidogen is required for proper regeneration of peripheral nerves after injury in vivo.


Nidogen plays a role in the regenerative axon growth of adult sensory neurons through Schwann cells.

Lee HK, Seo IA, Suh DJ, Park HT - J. Korean Med. Sci. (2009)

In vivo effect of nidogen inhibition on peripheral nerve regeneration. After sciatic nerve axotomy, AP or eTEM7-AP was infused using an Alzet mini-pump for 2 weeks and then the regenerative axons were stained with an anti-Tuj1 antibody. (A) The axonal morphology is high dystrophic in the eTEM7-treated group compared to the Fc-treated group. Scale bar; 100 µm. (B). The diameter of neurites in eTEM7-AP-treated group was thinner than that of AP controls. *P<0.05. (C). The mean lengths of regenerating neurites from AP and eTEMP7-AP-treated group showed no difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719197&req=5

Figure 3: In vivo effect of nidogen inhibition on peripheral nerve regeneration. After sciatic nerve axotomy, AP or eTEM7-AP was infused using an Alzet mini-pump for 2 weeks and then the regenerative axons were stained with an anti-Tuj1 antibody. (A) The axonal morphology is high dystrophic in the eTEM7-treated group compared to the Fc-treated group. Scale bar; 100 µm. (B). The diameter of neurites in eTEM7-AP-treated group was thinner than that of AP controls. *P<0.05. (C). The mean lengths of regenerating neurites from AP and eTEMP7-AP-treated group showed no difference.
Mentions: In order to find out an endogenous role of nidogen in peripheral nerve regeneration, we tried to block nidogen using recombinant ectodomain of tumor endothelial marker 7 (eTEM7). We previously showed that TEM7 is a possible transmembrane receptor for nidogen and that eTEM7 can specifically block nidogen function on Schwann cells without affecting laminin or fibronectin functions (19). After sciatic nerve axotomy, we continuously infused recombinant eTEM-AP or AP for 2 weeks using an Alzet mini-osmotic pump. The immunostaining of regenerative axons from proximal stumps of the axotomized sciatic nerves demonstrated that the regenerating axons of the eTEM7-AP-treated group showed signs of abnormal regenerative axon growth, compared to that of AP-treated controls. First, the regenerative axons looked fragile and dystrophic in eTEM7-AP-treated group (Fig. 3A). Second, the diameter of the regenerating axons was thinner in eTEM7-AP-treated group, compared to the AP-control (Fig. 3B). However, the mean length of the regenerating axons in eTEM7-AP-treated group (Fig. 3C) was not significantly shorter than controls. These findings suggest that nidogen is required for proper regeneration of peripheral nerves after injury in vivo.

Bottom Line: Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells.Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent.Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Dong-A University, Busan, Korea.

ABSTRACT
We previously reported that nidogen is an extracellular matrix protein regulating Schwann cell proliferation and migration. Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells. Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent. Continuous infusion of recombinant ectodomain of tumor endothelial marker 7, which specifically blocks nidogen function in Schwann cells, suppressed regenerative neurite growth in a sciatic nerve axotomy model. Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.

Show MeSH
Related in: MedlinePlus