FBXL6 is dysregulated in keloids and promotes keloid fibroblast growth by inducing c-Myc expression.

C-MYC-mediated keloid fibroblasts proliferation and collagen deposit may contribute to the development of keloids. F-box and leucine-rich repeat protein 6 (FBXL6) is reported to be involved in tumour progression, while the role of FBXL6 in keloid fibroblasts is not deciphered. Normal control skins, hypertrophic scars and keloid tissues were collected and prepared for FBXL6 detection. FBXL6 short hairpin RNAs (shRNAs) or FBXL6 over-expression plasmids were transfected into keloid fibroblasts, and then c-MYC plasmids were further transfected. Cell viability was assayed with a Cell-Counting Kit-8 kit. The relative expression of FBXL6, Cyclin A1, Cyclin D2, Cyclin E1 and Collagen I was detected with real-time PCR and Western blot. Elevated FBXL6 expression could be observed in keloid tissues and hypertrophic scars. FBXL6 shRNAs transfection could inhibit the viability of keloid fibroblasts with diminished c-MYC expression and down-regulated Cyclin A1, Cyclin D2, Cyclin E1 and Collagen I expression. At the same time, overexpressed FBXL6 could promote the proliferation of keloid fibroblasts. Overexpression of c-MYC could promote the proliferation of keloid fibroblasts reduced by FBXL6 shRNAs with up-regulated Cyclin A1 and Collagen I expression. FBXL6 could promote the growth of keloid fibroblasts by inducing c-MYC expression, which could be targeted in keloids treatment.

The deubiquitinating enzyme USP37 promotes keloid fibroblasts proliferation and collagen production by regulating the c-Myc expression.

Previous research testifies that c-Myc may promote keloid fibroblast proliferation and collagen accumulation. Ubiquitin-specific peptidase 37 (USP37)-mediated deubiquitination and stabilisation of c-Myc are vital for lung cancer proliferation, while the potential role of USP37 in keloid fibroblasts is not investigated. Elevated USP37, c-Myc, and Collagen I content were detected in keloid tissue with RT-PCR or ELISA assay. USP37 over-expression plasmids or USP37 short hairpin RNAs (shRNAs) were transfected into keloid fibroblasts with Lipofectamine 3000 to decipher the role of USP37 in keloid fibroblasts. USP37 overexpression could promote the proliferation of keloid fibroblasts with increased c-Myc and Collagen I expression. On the other hand, USP37 shRNAs inhibited the proliferation of keloid fibroblasts with diminished c-Myc and Collagen I expression. It was worth noting that C-Myc overexpression promoted the proliferation of keloid fibroblasts inhibited by USP37 shRNAs with increasing Collagen I expression. All of these results demonstrate that USP37 could regulate c-Myc to promote the proliferation and collagen deposit of keloid fibroblasts, and USP37 could be targeted in future keloid therapy.

Neural progenitor cell-derived nanovesicles promote hair follicle growth via miR-100.

BACKGROUND: Accumulating evidence shows that mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise to promote hair growth. However, large-scale production of EVs is still a challenge. Recently, exosome-mimetic nanovesicles (NV) prepared by extruding cells have emerged as an alternative strategy for clinical-scale production. Here, ReNcell VM (ReN) cells, a neural progenitor cell line was serially extruded to produce NV. RESULTS: ReN-NV were found to promote dermal papilla cell (DPC) proliferation. In addition, in a mouse model of depilation-induced hair regeneration, ReN-NV were injected subcutaneously, resulting in an acceleration of hair follicle (HF) cycling transition at the site. The underlying mechanism was indicated to be the activation of Wnt/ß-catenin signaling pathway. Furthermore, miR-100 was revealed to be abundant in ReN-NV and significantly up-regulated in DPCs receiving ReN-NV treatment. miR-100 inhibition verified its important role in ReN-NV-induced ß-catenin signaling activation. CONCLUSION: These results provide an alternative agent to EVs and suggest a strategy for hair growth therapy.

Recursive Paleohexaploidization Shaped the Durian Genome.

The durian (Durio zibethinus) genome has recently become available, and analysis of this genome reveals two paleopolyploidization events previously inferred as shared with cotton (Gossypium spp.). Here, we reanalyzed the durian genome in comparison with other well-characterized genomes. We found that durian and cotton were actually affected by different polyploidization events: hexaploidization in durian ∼19-21 million years ago (mya) and decaploidization in cotton ∼13-14 mya. Previous interpretations of shared polyploidization events may have resulted from the elevated evolutionary rates in cotton genes due to the decaploidization and insufficient consideration of the complexity of plant genomes. The decaploidization elevated evolutionary rates of cotton genes by ∼64% compared to durian and explained a previous ∼4-fold over dating of the event. In contrast, the hexaploidization in durian did not prominently elevate gene evolutionary rates, likely due to its long generation time. Moreover, divergent evolutionary rates probably explain 98.4% of reconstructed phylogenetic trees of homologous genes being incongruent with expected topology. The findings provide further insight into the roles played by polypoidization in the evolution of genomes and genes, and they suggest revisiting existing reconstructed phylogenetic trees.