Schwann cells (SCs), the primary glia in the peripheral nervous system (PNS), display remarkable plasticity in that fully mature SCs undergo dedifferentiation and convert to repair SCs upon nerve injury. Dedifferentiated SCs provide essential support for PNS regeneration by producing signals that enhance the survival and axon regrowth of damaged neurons, but the identities of neurotrophic factors remain incompletely understood. Here we show that SCs express and secrete progranulin (PGRN), depending on the differentiation status of SCs. PGRN expression and secretion markedly increased as primary SCs underwent dedifferentiation, while PGRN secretion was prevented by administration of cAMP, which induced SC differentiation. We also found that sciatic nerve injury, a physiological trigger of SC dedifferentiation, induced PGRN expression in SCs in vivo. These results suggest that dedifferentiated SCs express and secrete PGRN that functions as a paracrine factor to support the survival and axon growth of neighboring neurons after injury.
Bibliographical noteFunding Information:
information National Agenda Project of Korea National Research Council of Science and Technology, Grant/Award Number: NAP-09-04; National Research Council of Science and Technology, Grant/Award Number: CRC-15-04-KIST; Seoul National University, Research Institute for Veterinary Science; Seoul National University; Seoul National University, Grant/Award Number: 550-20180037; National Research Council of Science & Technology; National Research Foundation of Korea, Grant/Award Number: NRF-2018M3C7A1025485; National Research Council of Science & TechnologyWe would like to thank Prof. Hwan Tae Park (Dong-A University) for valuable comments on this study. This work was supported by grants from the National Agenda Project of Korea National Research Council of Science & Technology (NAP-09-04 to JKFS), National Research Foundation of Korea (NRF-2018M3C7A1025485 to EMH), National Research Council of Science & Technology of Korea (CRC-15-04-KIST to EMH), Research Resettlement Fund for the new faculty of Seoul National University (550-20180037 to EMH), and partially by the Research Institute for Veterinary Science at Seoul National University.
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience