Vitamins and their derivatives synergistically promote hair shaft elongation ex vivo via PlGF/VEGFR-1 signaling activation
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ABSTRACT:
PROVIDER: PRJNA837566 | ENA |
REPOSITORIES: ENA
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Project description:Background: Despite that vitamins or their derivatives (Vits), such as panthenyl ethyl ether, tocopherol acetate, or pyridoxine have been widely used in topical hair care products, their efficacy and mode of action have been insufficiently studied. Objective: To elucidate biological influence of Vits on hair follicles and dissect underlying mechanisms. Methods: Mouse vibrissa hair follicle organ culture model was utilized to evaluate the effects of Vits on hair shaft elongation. Gene and protein expression analyses, and histological investigation were conducted to elucidate responsible mechanisms. Human hair follicle cell culture was adopted to assess clinical relevance. Results: In organ culture models, the combination of panthenyl ethyl ether, tocopherol acetate, and pyridoxine (namely PPT) supplementation significantly promoted hair shaft elongation. PPT-treatment enhanced hair matrix cell proliferation by 1.9 folds compared to controls, as demonstrated by Ki-67 positive immunoreactivity. PPT-treated mouse dermal papillae up-regulated Placental growth factor (Plgf) by 1.6 folds, compared to non-treated controls. Importantly, addition of PlGF neutralizing antibodies to the ex vivo culture diminished the promotive effect on hair growth and the increase in VEGFR1 phosphorylation achieved by PPT. A VEGFR1 inhibitor also repressed the promotion of hair shaft elongation. Microarray analysis suggested synergistic summation of individual Vit bioactivity, putatively explaining the effect of PPT. Moreover, PPT increased PlGF secretion in cultured human dermal papilla cells. Conclusion: Our findings suggested that PPT promoted hair shaft elongation via activating PlGF/VEGFR-1 signaling. The current study can shed light on the previously underrepresented advantage of utilizing Vits for ameliorating hair care products.
2022-06-30 | GSE202865 | GEO
Project description:We have used a chimeric VEGFR-2 in which the extracellular domain of mouse VEGFR-2 was replaced with the extracellular domain of human CSF-1 receptor. VEGFR-2 was immunoprecipitated with anti-VEGFR-2 antibody from PAE cells ectopically expressing VEGFR-2. The immunoprecipitated proteins were eluted and separated on SDS-PAGE, followed by in-gel chymotrypsin or trypsin digestion. The digested samples were analyzed by nano LC/MS/MS on a Thermo Fisher LTQ Orbitrap XL. The LC-MS/MS data were analyzed using Proteome Discoverer (Thermo Fisher Scientific; Version 1.3.0.339). MS/MS search was carried out using Sequest search algorithm against the sequence of target mouse protein from the UniProtKB database. Search parameters included chymotrypsin as the enzyme with four missed cleavage allowed; methylation at lysine and arginine, phosphorylation of serine, threonine, and tyrosine, alkylation at cysteine, and oxidation of methionine were set as dynamic modifications. Precursor and fragment mass tolerance were set to 5 ppm and 0.8 Da, respectively. The false discovery rate was calculated by enabling the peptide sequence analysis using a decoy database. High confidence peptide identifications were obtained by setting a target false discovery rate threshold of 1% at the peptide level.
2019-11-22 | PXD000520 | Pride
Project description:Melanoma growth is driven by malignant melanoma initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member, ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE-1 and are associated with CD31-negative vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced in a VEGFR-1-dependent manner expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1, but not in ABCB5- bulk populations that were predominantly VEGFR-1-negative. In vivo, melanomaspecific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen, laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results demonstrate that VEGFR-1 function in MMIC regulates VM and associated laminin production, and show that this function represents one mechanism through which MMIC promote tumor growth.
2011-01-13 | GSE26569 | GEO
Project description:Melanoma growth is driven by malignant melanoma initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member, ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE-1 and are associated with CD31-negative vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced in a VEGFR-1-dependent manner expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1, but not in ABCB5- bulk populations that were predominantly VEGFR-1-negative. In vivo, melanomaspecific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen, laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results demonstrate that VEGFR-1 function in MMIC regulates VM and associated laminin production, and show that this function represents one mechanism through which MMIC promote tumor growth. Microarray analyses were performed on purified ABCB5+ (n=5) and ABCB5- (n=5) cell subsets derived from the established human melanoma cell lines G3361 and A375 and from three distinct clinical melanoma specimen. Total RNA was extracted, processed and hybridized onto Affymetrix human HG-U133Plus2 GeneChip microarrays (Affymetrix, Santa Clara, CA).
2011-01-13 | E-GEOD-26569 | biostudies-arrayexpress
Project description:EGFR and hair shaft differentiation
| PRJNA527731 | ENA
Project description:Therapeutic resistance to VEGFR signaling inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the contribution of stromal and tumor cells to resistance of NSCLC to VEGFR tyrosine kinase inhibitors (TKIs). Gene expression analysis of stromal (mouse) and tumor (human) compartments enabled us to identify the HGF/c-MET pathway as a driver and a potential biomarker of VEGFR TKI resistance.
2017-07-06 | GSE64472 | GEO
Project description:Transcriptional profiling of bulk-tumor samples left untreated or treated with TH-302, VEGFR-2 blockade, or the combination
2023-11-20 | GSE220217 | GEO
Project description:Rationale: VEGF family members mediate their effects through cell surface receptors VEGFR-1, VEGFR-2 and NRP. Specific ligands were used to stimulate specific combinations of the receptors to evaluate ligand and receptor properties. Objective: The properties of a novel VEGF family member Vammin were studied in level of receptor binding, gene expression in HUVECs by RNAseq and in vivo using adenoviral gene trasfers. Methods: HUVECs were trasduced using adenoviral vectors encoding VEGF-A109, VEGF-A165 and Vammin and with an empty vector as a control. Gene expression was measured using RNA sequencing. Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Results and conclusions: Vammin is a highly effective VEGFR2 ligand that induces differential gene expression of genes related to proliferation, survival, angiogenesis and blood vessel development in HUVECs. The effect is stronger than ones induced by VEGF-A165 and VEGF-A109. Vammin induces highly efficient angiogenic responses when delivered into rabbit skeletal muscles using adenoviral gene transfers.
2017-08-11 | GSE68535 | GEO
Project description:Combined VEGFR and MAPK pathway inhibition in angiosarcoma
| PRJNA693791 | ENA
Project description:Developing strategies to overcome the frequent resistance to VEGF/VEGFR inhibitors in patients is a major challenge in antiangiogenic therapy for cancer. Targeting the VEGF pathway in vivo induces hypoxia and therefore enables to study drug-induced hypoxia in tumors. Hypoxia also occurs in the spontaneous evolution of cancers, particularly around areas of necrosis. Using cell markers such as CD133, CXCR4, or ALDH1, we identified stem-like cells in peri-necrotic areas in human biopsies and xenografts models of renal cancers. These stem-like cells were able in vitro to self-renew, form carcinoma spheres and had a tumorigenic potency, thus showing characteristics of stem-like cancer cells. In xenografted human renal cell carcinoma, we further demonstrated a strong link between necrosis, either spontaneous or treatment-induced, and the presence of CD133/CXCR4 double positive stem-like cells. Hypoxia increased their tumorigenic potency, induced overexpression of metallothionein2A, which we here identified as critical regulator of resistance to VEGFR-inhibition.
2014-12-31 | GSE32414 | GEO