Hypertrophic scar is a dermal fibroproliferative disease characterized by the overproduction and deposition of extracellular matrix, and the hyperproliferation and enhanced angiogenesis of fibroblasts, along with their enhanced differentiation to myofibroblasts. Botulinum toxin type A shows potential for prevention of hypertrophic scar formation; however, its effectiveness in attenuating skin fibrosis and the related mechanism are unclear. In this study, human scar fibroblasts were cultured and stimulated with botulinum toxin type A, and the changes in fibroblast proliferation, migration, and protein expression of pro-fibrotic factors were evaluated with colorimetric, scratch, and enzyme-linked immunosorbent assays and western blotting, respectively. Botulinum toxin type A treatment decreased the proliferation and migration of human scar fibroblasts compared with those of untreated controls. Protein expression levels of pro-fibrotic factors (transforming growth factor β1, interleukin-6, and connective tissue growth factor) were also inhibited by botulinum toxin type A, whereas the JNK phosphorylation level was increased. Activation of the JNK pathway demonstrated the inhibitory effects of the toxin on human scar fibroblast proliferation and production of pro-fibrotic factors, suggesting that the suppressive effects of botulinum toxin type A are closely associated with JNK phosphorylation. Overall, this study showed that botulinum toxin type A has a suppressive effect on extracellular matrix production and scar-related factors in human scar fibroblasts in vitro, and that regulation of JNK signaling plays an important role in this process. Our results provide a theoretical basis, at the cellular level, for the therapeutic use of botulinum toxin type A.
Summary Background Platelet‐rich plasma (PRP) is a blood fraction that contains high concentrations of several growth factors. PRP has been recently used in skin wound healing and rejuvenation. However, the precise molecular mechanisms underlying PRP‐induced wound healing are unknown. Aims This study aimed to evaluate the effects of PRP on extracellular matrix remodeling, which requires the activation of dermal fibroblasts. Methods Cell proliferation and migration assay, enzyme‐linked immunosorbent analysis, and Western blotting were performed on PRP‐treated human skin fibroblasts. Results Platelet numbers were enhanced by 4.6‐fold in PRP compared to that in whole blood. PRP stimulated the proliferation and migration of human dermal fibroblasts and increased the expression of human procollagen I alpha 1, elastin, MMP‐1, and MMP‐2 in human dermal fibroblasts. PRP‐treated human dermal fibroblasts also showed a dramatic reduction in the phosphorylation of c‐Jun N‐terminal kinase (JNK), whereas total JNK levels were not significantly reduced. Conclusions Collectively, PRP induced increased expression of type I collagen, elastin, MMP‐1, and MMP‐2, thereby accelerating wound healing. Our findings reveal basic mechanisms underlying PRP‐mediated tissue remodeling. Thus, these results could be exploited for clinical dermatology and skin rejuvenation.
Classical swine fever virus (CSFV) causes a highly contagious disease among swine that has an important economic impact worldwide. CSFV strain LOM is an attenuated virus of low virulent strain of Miyagi isolated from Japan in 1956. Eight DNA fragments representing the genome of the CSFV strain LOM were obtained by RT-PCR. These were used to determine the complete nucleotide sequence and construct a full-length cDNA clone which was called Flc-LOM. Sequence analysis of the recombinant clone (Flc-LOM) revealed the presence of eight mutations, resulting in two amino acid substitutions, when compared to the parental sequence. RNA transcripts of both LOM and Flc-LOM were directly infectious in PK-15 cells. The rescued Flc-LOM virus grew more slowly than the parental virus, LOM, in the cells. Intramuscular immunization with Flc-LOM was safe and highly immunogenic in pigs; no clinical signs or virus transmission to sentinel animals were observed after 35 days. CSFV-specific neutralizing antibodies were detected 14 days post-infection. After challenge with the virulent CSFV strain SW03, pigs immunized with Flc-LOM were shown to be fully protected. Thus, our newly established infectious clone of CSFV, Flc-LOM, could serve as a vaccine candidate.
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