Abstract
Schwann cells experience de-differentiation, proliferation, migration, re-differentiation and myelination, and participate in the repair and regeneration of injured peripheral nerves. Our previous sequencing analysis suggested that the gene expression level of matrix metalloproteinase 7 (MMP7), a Schwann cell-secreted proteolytic enzyme, was robustly elevated in rat sciatic nerve segments after nerve injury. However, the biological roles of MMP7 are poorly understood. Here, we exposed primary cultured Schwann cells with MMP7 recombinant protein and transfected siRNA against MMP7 into Schwann cells to examine the effect of exogenous and endogenous MMP7. Meanwhile, the effects of MMP7 in nerve regeneration after sciatic nerve crush in vivo were observed. Furthermore, RNA sequencing and bioinformatic analysis of Schwann cells were conducted to show the molecular mechanism behind the phenomenon. In vitro studies showed that MMP7 significantly elevated the migration rate of Schwann cells but did not affect the proliferation rate of Schwann cells. In vivo studies demonstrated that increased level of MMP7 contributed to Schwann cell migration and myelin sheaths formation after peripheral nerve injury. MMP7-mediated genetic changes were revealed by sequencing and bioinformatic analysis. Taken together, our current study demonstrated the promoting effect of MMP7 on Schwann cell migration and peripheral nerve regeneration, benefited the understanding of cellular and molecular mechanisms underlying peripheral nerve injury, and thus might facilitate the treatment of peripheral nerve regeneration in clinic.
Highlights
Peripheral nerve injury is a common clinical issue that substantially affects patients’ quality of life and leads to severe social and economic burdens [1]
Schwann cells transfected with matrix metalloproteinase 7 (MMP7) siRNA1 or MMP7 siRNA2 did not exhibit altered proliferation rate as compared with cells transfected with the non-targeting negative control (Fig. 1c, d, e, and h)
We examined the biological effects of matrilysin MMP7 by using primary cultured Schwann cells and rat sciatic nerve crush model
Summary
Peripheral nerve injury is a common clinical issue that substantially affects patients’ quality of life and leads to severe social and economic burdens [1]. Treatments of peripheral nerve injury, including nerve suturing, autologous nerve grafting, and tissue engineered nerve transplantation, facilitated the functional recovery of injured nerve [2, 3]. Gaining a deeper understanding of the cellular and molecular mechanisms underlying peripheral nerve injury will benefit the clinical treatment of peripheral nerve injury and is in a pressing need. Schwann cells sense injury signal, switch to a proliferating state, migrate to the injured site to clear axon and myelin debris and build bands of Büngner. Schwann cells redifferentiate to a myelinating state and ensheath regenerated axons [6, 7]. Schwann cells secret neurotrophic factors to propel axon regrowth as well as proteolytic enzymes to re-organize extracellular matrix and generate a suitable extrinsic environment for nerve regeneration [8,9,10]
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