LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

The activation of GIP/GIPR axis via Sonic hedgehog signaling promotes the bridging of gapped nerves in sciatic nerve injury.

Photo by lunarts from unsplash

Schwann cells play an essential role in peripheral nerve regeneration by generating a favorable microenvironment. Gastric inhibitory peptide/ gastric inhibitory peptide receptor (GIP/GIPR) axis deficiency leads to failure of sciatic… Click to show full abstract

Schwann cells play an essential role in peripheral nerve regeneration by generating a favorable microenvironment. Gastric inhibitory peptide/ gastric inhibitory peptide receptor (GIP/GIPR) axis deficiency leads to failure of sciatic nerve repair. However, the underlying mechanism remains elusive. In this study, we surprisingly found that GIP treatment significantly enhances the migration of Schwann cells and the formation of Schwann cell cords during recovery from sciatic nerve injury in rats. We further revealed that GIP and GIPR levels in Schwann cells were low under normal conditions, and significantly increased after injury demonstrated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Wound healing and Transwell assays showed that GIP stimulation and GIPR silencing by blocking antibody could affect Schwann cell migration. In vitro and in vivo mechanistic studies based on interference experiment revealed that GIP/GIPR might promote mechanistic target of rapamycin complex 2 (mTORC2) activity, thus facilitating cell migration; Rap1 activation might be involved in this process. Finally, we retrieved the stimulatory factors responsible for GIPR induction after injury. The results indicate that sonic hedgehog (SHH) is a potential candidate whose expression increased upon injury. Luciferase and chromatin immunoprecipitation (ChIP) assays showed that Gli3, the target transcription factor of the SHH pathway, dramatically augmented GIPR expression. Additionally, in vivo inhibition of SHH could effectively reduce GIPR expression after sciatic nerve injury. Collectively, our study reveals the importance of GIP/GIPR signaling in Schwann cell migration, providing a therapeutic avenue toward peripheral nerve injury.

Keywords: sciatic nerve; schwann; gip gipr; gipr; nerve injury; injury

Journal Title: Journal of neurochemistry
Year Published: 2023

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.