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Research article
Sheng Yi
Nantong University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1316-3370
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background Growth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve injury and regeneration. Our previous sequencing analysis found that betacellulin (Btc), an epidermal growth factor protein family member, showed elevated mRNA expressions in the nerve segment after rat peripheral nerve injury, implying the potential involvement of Btc during peripheral nerve repair.
Methods Expression of Btc was examined in Schwann cells. The role of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or exposed cultured cells with Btc recombinant protein, respectively. The biological functions of Schwann cell-secreted Btc on neurons were also determined. Moreover, the in vivo effect of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated.
Results Immunostaining images and ELISA readings showed Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that siRNA against Btc impeded Schwann cell migration while exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells might influence neuron behavior and affect axon length. In vivo evidence showed that Btc enhanced axonal regrowth and nerve regeneration after both rat sciatic nerve crush injury and transection injury.
Conclusion Our findings demonstrated Btc-mediated Schwann cell-axon interactions, revealed the essential roles of Btc on Schwann cell migration and axon elongation, and implied the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.
Keywords
peripheral nerve injury, betacellulin, Schwann cell migration, axon elongation, nerve regeneration
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CURRENT STATUS: Under Review
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Posted 13 Mar, 2021
Review #2 received
Received 13 Mar, 2021
Reviewer #2 agreed
On 03 Mar, 2021
Editor assigned
On 01 Mar, 2021
Reviewers invited
Invitations sent on 01 Mar, 2021
Reviewer #1 agreed
On 01 Mar, 2021
Review #1 received
Received 01 Mar, 2021
Submission checks complete
On 01 Mar, 2021
Editor invited
On 01 Mar, 2021
This version was not preprinted
Version 1
Posted 05 Feb, 2021
No community comments so far
Review #1 received
Received 19 Feb, 2021
Editorial decision: Major revision
On 19 Feb, 2021
Review #2 received
Received 18 Feb, 2021
Reviewer #2 agreed
On 06 Feb, 2021
Reviewer #1 agreed
On 05 Feb, 2021
Reviews received
Received 05 Feb, 2021
Reviewers invited
Invitations sent on 03 Feb, 2021
Editor invited
On 27 Jan, 2021
Editor assigned
On 27 Jan, 2021
Submission checks complete
On 27 Jan, 2021
First submitted
On 25 Jan, 2021
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This preprint is under consideration at Molecular Medicine. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Sheng Yi
Nantong University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1316-3370
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 13 Mar, 2021
Review #2 received
Received 13 Mar, 2021
Reviewer #2 agreed
On 03 Mar, 2021
Editor assigned
On 01 Mar, 2021
Reviewers invited
Invitations sent on 01 Mar, 2021
Reviewer #1 agreed
On 01 Mar, 2021
Review #1 received
Received 01 Mar, 2021
Submission checks complete
On 01 Mar, 2021
Editor invited
On 01 Mar, 2021
This version was not preprinted
Version 1
Posted 05 Feb, 2021
No community comments so far
Review #1 received
Received 19 Feb, 2021
Editorial decision: Major revision
On 19 Feb, 2021
Review #2 received
Received 18 Feb, 2021
Reviewer #2 agreed
On 06 Feb, 2021
Reviewer #1 agreed
On 05 Feb, 2021
Reviews received
Received 05 Feb, 2021
Reviewers invited
Invitations sent on 03 Feb, 2021
Editor invited
On 27 Jan, 2021
Editor assigned
On 27 Jan, 2021
Submission checks complete
On 27 Jan, 2021
First submitted
On 25 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background Growth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve injury and regeneration. Our previous sequencing analysis found that betacellulin (Btc), an epidermal growth factor protein family member, showed elevated mRNA expressions in the nerve segment after rat peripheral nerve injury, implying the potential involvement of Btc during peripheral nerve repair.
Methods Expression of Btc was examined in Schwann cells. The role of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or exposed cultured cells with Btc recombinant protein, respectively. The biological functions of Schwann cell-secreted Btc on neurons were also determined. Moreover, the in vivo effect of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated.
Results Immunostaining images and ELISA readings showed Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that siRNA against Btc impeded Schwann cell migration while exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells might influence neuron behavior and affect axon length. In vivo evidence showed that Btc enhanced axonal regrowth and nerve regeneration after both rat sciatic nerve crush injury and transection injury.
Conclusion Our findings demonstrated Btc-mediated Schwann cell-axon interactions, revealed the essential roles of Btc on Schwann cell migration and axon elongation, and implied the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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