Background: Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results: We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions: In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

Reverting activated hepatic stellate cells (HSCs) to less activation or quiescent status is a promising strategy for liver fibrosis. Histone deacetylase inhibitor (HDACI) could suppress HSCs activation. Our previous study demonstrated a critical role of miRNAs in HSCs activation. Here, we explored the involvement of miRNAs in HDACI induced HSCs deactivation. Human cell line LX2 that resembled activated HSCs was treated with an HDACI - valproic acid (VPA). The effects of VPA on the protein and miRNA profile of LX2 were comprehensively analyzed by iTraq quantitative proteomics and miRNA microarray. The interaction between miRNA and proteins was investigated systematically. The biofunctions of differentially expressed proteins and miRNA targeted proteins were annotated. VPA treatment attenuated the activation phenotype of LX2. In VPA treated LX2, among 1548 quantified proteins, only 86 proteins were differentially expressed (VPA-proteins). While among 282 high-abundance miRNAs, 123 were differentially expressed (VPA-miRNAs), with 104 down-regulated and 19 up-regulated. The top biofunctions of VPA-proteins were closely related to HSCs activation, including cell death and survival, cell movement, cellular growth and proliferation. Furthermore, 22 out of the 36 VPA-proteins involved in cell death and survival, and 19 out of the 30 VPA-proteins involved in cellular movement were predicted targets of VPA-miRNAs. A direct regulatory effect of histone acetylation on miRNA expression was also established. In conclusion, our data provided the molecular mechanisms for VPA induced HSCs deactivation at the protein level and suggested crosstalk between histone acetylation and miRNAs in the inhibitory effects of HDACI on HSCs activation.

Background: Cohen syndrome (CS) is a clinically heterogeneous disorder characterized by extensive phenotypic variation with autosomal recessive inheritance. VPS13B was identified to be the disease-causing gene for CS. The objectives of the present study were to screen likely pathogenic mutations of the patient with developmental delay and mental retardation, and to determinate the effect of this splice-site mutation by reverse transcription analysis.Methods: Whole exome sequencing (WES) in combination with Sanger sequencing were performed to identify the causative mutations of this CS family. Subsequently, the impact of the intronic variant on splicing was analyzed by reverse transcription and the construction of expression vector.Results: A novel homozygous splice-site mutation (c.6940+1G>T) in the VPS13B gene was identified in this proband. Sanger sequencing analysis of the cDNA demonstrated that the c.6940+1G>T variant could cause the skipping of entire exon 38, resulting in the loss of 208 nucleotides and further give rise to the generation of a premature in-frame stop codon at code 2,247.Conclusions: The homozygous VPS13B splicing variant c.6940+1G>T was co-segregated with the CS phenotypes in this family and was identified to be the cause of CS after comprehensive consideration of the clinical manifestations, genetic analysis and cDNA sequencing result.