TWEAK increases angiogenesis to promote diabetic skin wound healing by regulating Fn14/EGFR signaling.

OBJECTIVE: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of tumor necrosis factor superfamily, can bind to fibroblast growth factor-inducible 14 (Fn14) receptor and stimulate angiogenesis. The interaction between epidermal growth factor receptor (EGFR) and endothelial growth factor (EGF) leads to EGFR signal transduction and promotes angiogenesis. The objective of this study was to explore whether TWEAK participated in the diabetic skin wound healing by regulating Fn14/EGFR signaling. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with 35 mmol/L d-glucose and classified into the Control Group, High Glucose (HG) Group and HG + TWEAK Group. Then, the TWEAK expression and the proliferation, migration and tubule formation of HUVECs were detected, respectively. In vivo experiment, the diabetic model was established by injecting streptozotocin (STZ, 50 mg/kg) into male BALB/c mice. On the back of successfully modeled diabetic mice, a full-thickness skin wound of 6 mm diameter was formed. Then, the mice were randomly assigned into three groups: Blank Group, Phosphate Buffer Saline (PBS) Group, and TWEAK Group. Subsequently, expression levels of TWEAK, Fn14, EGFR and vascular endothelial growth factor (VEGF)-A were measured, and the CD31 expression in the wounded skin tissue of mice was checked by immunohistochemistry staining. RESULTS: The expression level of TWEAK in HUVECs of HG Group decreased significantly, as well as the viability, migration, and tubule formation of cells. After over-expression of TWEAK, the cell viability, migration, and tubule formation abilities of HUVECs recovered remarkably. In vivo, the wound healing rate of diabetic mice was raised, the neovascularization was increased, and the CD31 expression in the wounded tissue was obviously upregulated after injection with recombinant TWEAK antibody. CONCLUSION: TWEAK stimulates angiogenesis and accelerates the wound healing of diabetic skin by regulating Fn14/EGFR signaling.

Naringin acts as a TRPV1 antagonist to attenuate UVB-induced senescence and damage in HaCaT cells.

This study aimed to explore the mechanism of naringin (Nar) in alleviating ultraviolet B (UVB)-induced HaCaT cell senescence and damage. Human keratinocytes (HaCaT cells) were divided into control, UVB, UVB + Nar, UVB + Cap, and UVB + Nar + Cap groups. Analysis was performed using the MTT assay to assess cell viability, flow cytometry to measure the apoptosis level, SA-ß-Gal staining to observe cellular senescence, and Western blot to assess protein levels of TRPV1, p16, p53, p21, matrix metalloproteinase (MMP)-1, and MMP-9. Both UVB irradiation and capsaicin (Cap) treatment upregulated the expression of TRPV1 in HaCaT cells, inhibited cell proliferation, promoted apoptosis, and increased the expression of p16, p53, p21, MMP-1, and MMP-9. Nar treatment reversed the above effects via inhibition of TRPV1 expression, thereby relieving senescence and cell damage induced by UVB irradiation. Taken together, these findings suggest that Nar can reduce UVB-induced senescence and damage in HaCaT cells by acting as an antagonist of TRPV1.

Evolutionary origin and establishment of a dioecious diploid-tetraploid complex.

Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants. Here we test the hypothesis that a stable sex-determination system and spatial/ecological isolation facilitate the establishment of dioecious polyploids. We determined the ploidy levels of 351 individuals from 28 populations of the dioecious species Salix polyclona, and resequenced 190 individuals of S. polyclona and related taxa for genomic diversity analyses. The ploidy survey revealed a frequency 52% of tetraploids in S. polyclona, and genomic k-mer spectra analyses suggested an autopolyploid origin for them. Comparisons of diploid male and female genomes identified a female heterogametic sex-determining factor on chromosome 15, which probably also acts in the dioecious tetraploids. Phylogenetic analyses revealed two diploid clades and a separate clade/grade of tetraploids with a distinct geographic distribution confined to western and central China, where complex mountain systems create higher levels of environmental heterogeneity. Fossil-calibrated phylogenies showed that the polyploids emerged during 7.6-2.3 million years ago, and population demographic histories largely matched the geological and climatic history of the region. Our results suggest that inheritance of the sex-determining system from the diploid progenitor as intrinsic factor and spatial isolation as extrinsic factor may have facilitated the preservation and establishment of polyploid dioecious populations.

The phylogeny of Salix revealed by whole genome re-sequencing suggests different sex-determination systems in major groups of the genus.

BACKGROUND AND AIMS: The largest genus of Salicaceae sensu lato, Salix, has been shown to consist of two main clades: clade Salix, in which species have XY sex-determination systems (SDSs) on chromosome 7, and clade Vetrix including species with ZW SDSs on chromosome 15. Here, we test the utility of whole genome re-sequencing (WGR) for phylogenomic reconstructions of willows to infer changes between different SDSs. METHODS: We used more than 1 TB of WGR data from 70 Salix taxa to ascertain single nucleotide polymorphisms on the autosomes, the sex-linked regions (SLRs) and the chloroplast genomes, for phylogenetic and species tree analyses. To avoid bias, we chose reference genomes from both groups, Salix dunnii from clade Salix and S. purpurea from clade Vetrix. KEY RESULTS: Two main largely congruent groups were recovered: the paraphyletic Salix grade and the Vetrix clade. The autosome dataset trees resolved four subclades (C1-C4) in Vetrix. C1 and C2 comprise species from the Hengduan Mountains and adjacent areas and from Eurasia, respectively. Section Longifoliae (C3) grouped within the Vetrix clade but fell into the Salix clade in trees based on the chloroplast dataset analysis. Salix triandra from Eurasia (C4) was revealed as sister to the remaining species of clade Vetrix. In Salix, the polyploid group C5 is paraphyletic to clade Vetrix and subclade C6 is consistent with Argus's subgenus Protitea. Chloroplast datasets separated both Vetrix and Salix as monophyletic, and yielded C5 embedded within Salix. Using only diploid species, both the SLR and autosomal datasets yielded trees with Vetrix and Salix as well-supported clades. CONCLUSION: WGR data are useful for phylogenomic analyses of willows. The different SDSs may contribute to the isolation of the two major groups, but the reproductive barrier between them needs to be studied.

Chromosome-scale assembly of the genome of Salix dunnii reveals a male-heterogametic sex determination system on chromosome 7.

Sex determination systems in plants can involve either female or male heterogamety (ZW or XY, respectively). Here we used Illumina short reads, Oxford Nanopore Technologies (ONT) long reads and Hi-C reads to assemble the first chromosome-scale genome of a female willow tree (Salix dunnii), and to predict genes using transcriptome sequences and available databases. The final genome sequence of 328 Mb in total was assembled in 29 scaffolds, and includes 31,501 predicted genes. Analyses of short-read sequence data that included female and male plants suggested a male heterogametic sex-determining factor on chromosome 7, implying that, unlike the female heterogamety of most species in the genus Salix, male heterogamety evolved in the subgenus Salix. The S. dunnii sex-linked region occupies about 3.21 Mb of chromosome 7 in females (representing its position in the X chromosome), probably within a pericentromeric region. Our data suggest that this region is enriched for transposable element insertions, and about one-third of its 124 protein-coding genes were gained via duplications from other genome regions. We detect purifying selection on the genes that were ancestrally present in the region, though some have been lost. Transcriptome data from female and male individuals show more male- than female-biased genes in catkin and leaf tissues, and indicate enrichment for male-biased genes in the pseudo-autosomal regions. Our study provides valuable genomic resources for further studies of sex-determining regions in the family Salicaceae, and sex chromosome evolution.