Regulation of Schwann cell proliferation and migration by miR-1 targeting brain-derived neurotrophic factor after peripheral nerve injury

Abstract

Peripheral nerve injury is a global problem that causes disability and severe socioeconomic burden. Brain-derived neurotrophic factor (BDNF) benefits peripheral nerve regeneration and becomes a promising therapeutic molecule. In the current study, we found that microRNA-1 (miR-1) directly targeted BDNF by binding to its 3′-UTR and caused both mRNA degradation and translation suppression of BDNF. Moreover, miR-1 induced BDNF mRNA degradation primarily through binding to target site 3 rather than target site 1 or 2 of BDNF 3′-UTR. Following rat sciatic nerve injury, a rough inverse correlation was observed between temporal expression profiles of miR-1 and BDNF in the injured nerve. The overexpression or silencing of miR-1 in cultured Schwann cells (SCs) inhibited or enhanced BDNF secretion from the cells, respectively, and also suppressed or promoted SC proliferation and migration, respectively. Interestingly, BDNF knockdown could attenuate the enhancing effect of miR-1 inhibitor on SC proliferation and migration. These findings will contribute to the development of a novel therapeutic strategy for peripheral nerve injury, which overcomes the limitations of direct administration of exogenous BDNF by using miR-1 to regulate endogenous BDNF expression.

Characteristics of tendon derived stem cells according to different factors to induce the tendinopathy

“…Although the exact mechanism is not clear, quinolone may produce and accumulate reactive oxygen species, altering the proliferative function of cells (Kirchgesner et al, ). In contrast, previous studies (Han et al, ; Yi et al, ) have shown that injury promotes cell proliferation, which may help explain our results. Zhang and Wang, stimulated TDSCs mechanically, resulting in a high proliferation rate that is consistent with our results.…”

Ingenuity Pathway Analysis of Gene Expression Profiles in Distal Nerve Stump following Nerve Injury: Insights into Wallerian Degeneration

“…BDNF is a well-known neurotrophic factor that promotes neuronal survival and activity and stimulates axon growth (Braun et al, 1996; Lykissas et al, 2007). We have previously reported on the up-regulation of the mRNA expression of BDNF at 1, 4, 7, and 14 days post nerve crush injury (Yi et al, 2016). It has been known that after peripheral nerve injury, Schwann cells not only proliferate to form the bands of Bungner, but also produce a range of neurotrophic factors, including BDNF (Frostick et al, 1998; Faroni et al, 2013; Jang et al, 2016).…”

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

“…Inhibit proliferation and migration miR-182 [54]; let-7 [55]; miR-1 [56] Promote proliferation and migration miR-221, miR-222 [57] Cell type and function ncRNAs Inhibit migration miR-9 [58] Promote migration miR-132 [59] Regulate dedifferentiation and proliferation miR-34a [60] Regulate myelination miR-140 [60]; miR-29a [61] Regulate fibrinolysis miR-340 [ [83][84][85][86] miR-27b, miR-224 [87]; miR-574-3p, miR-31 [88] Inhibit proliferation miR-34, siRNA-P63 [89]; miR-720 [90]; miR-210, siRNA-E 2 F 3 [91] Improve proliferation, reduce differentiation miR-125b, siRNA-FGFR 2 [92,93] Inhibit proliferation, induce differentiation miR-24, siRNA-PAK4 [94] Keratinocytes Improve migration miR-205 [95][96][97] Inhibit migration, improve proliferation miR-483-3p [98] Inhibit migration miR-198 [99] Improve migration, inhibit migration miR-21 [100,101] Improve migration and proliferation miR-31, siRNA-EMP-1, siRNA-TGF-β [102] Regulate apoptosis lncRNA-p21 [103] Fibroblasts Inhibit proliferation let-7, miR-125 [104] Improve proliferation miR-29 [104]; miR-21 [105]; miR-22 [106]; lncRNA-H19 [107] Induce senescence miR-152, miR-181a [108]; miR-141 [109]; miR-143 [110]; miR-519a [11...…”

“…In addition, NGF expression that is inhibited by let-7 miRNA can regulate miR-221/222 expression in order to affect the SC phenotype, suggesting that a cascade of let-7 miRNA, through NGF, to miR-221/222 may represent a bypass for the let-7 regulation of SC phenotype modulation. Another neurotrophin, BDNF, is regulated by miR-1, and miR-1 regulates the proliferation and migration of SCs [56].…”