Hair growth promotion by necrostatin-1s.
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ABSTRACT:
SUBMITTER: Zheng M
PROVIDER: S-EPMC7573580 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), ?-catenin, insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups had higher hair covered skin ratio (100 ± 0.00%) than oral PMRP groups (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression.
| S-EPMC4534627 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s). Seven days after aneurysm induction by elastase perfusion, mice were randomly administered DMSO, Nec-1 (3.2?mg/kg/day) and Nec-1s (1.6?mg/kg/day) via intraperitoneal injection. Upon sacrifice on day 14 postaneurysm induction, the aortic expansion in the Nec-1s group (64.12?±?4.80%) was significantly smaller than that of the DMSO group (172.80?±?13.68%) (P?<?0.05). The mean aortic diameter of Nec-1 treated mice appeared to be smaller (121.60?±?10.40%) than the DMSO group, though the difference was not statistically significant (P?=?0.1). Histologically, the aortic structure of Nec-1s-treated mice appeared normal, with continuous and organized elastin laminae and abundant ?Actin-expressing SMCs. Moreover, Nect-1s treatment diminished macrophage infiltration and MMP9 accumulation and increased aortic levels of tropoelastin and lysyl oxidase. Together, our data suggest that pharmacological inhibition of necroptosis with Nec-1s stabilizes pre-existing aneurysms by diminishing inflammation and promoting connective tissue repair.
| S-EPMC5301478 | biostudies-literature
Project description:Hair loss and predominantly female hair loss is a common dermatologic condition with serious psychosocial consequences. Effective treatments remain scarce mainly due to the multifactorial elements involved in the onset of this chronic condition. The approved drugs available are based on molecules designed towards a single pharmacological target and do not interact with the various biochemical mechanisms involved in alopecia. Phytochemical compounds and their derivatives represent a plethora of biologically active agents, which act in synergism and simultaneously activate different biochemical pathways. Here we present an herbal formulation composed of herbs, vitamins, and minerals acting on hair regrowth and hair micro vascularization. This study aimed at evaluating the potential of Phyllotex™ to treat multifactorial androgenetic alopecia (AGA) in males and females, as well as delving into its molecular mechanisms of action. In vitro studies showed that the herbal formula stimulates cell proliferation of both dermal papilla and HaCaT cells and increases the phosphorylated form of the extracellular signal-regulated kinase 1 and 2 (ERK1/2), a well-known marker for cell proliferation. Surprisingly, expression of TGF-β1 was significantly suppressed without blocking DHT production. Additionally, the formula was able to rescue cells from the oxidative stress conditions generated by 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH), a high oxidative agent. This data supports the potential use of this formulation as a hair growth-promoting agent for the treatment of both male and female AGA due to its multifactorial composition, which grants it the ability to cope with the different mechanisms involved in alopecia.
| S-EPMC8426528 | biostudies-literature
Project description:Background: Kartogenin is a heterocyclic compound able to promote the proliferation, migration, and differentiation of various cell types and induce cartilage-like tissue regeneration. However, the role of kartogenin in hair follicles (HFs), remains unknown. We therefore investigated the effects of kartogenin on the regulation of hair growth and hair growth cycle transition. Methods: The effects of kartogenin on the proliferation, cell cycle status, and migration of primary human outer root sheath cells (ORSCs) were evaluated by MTS assay, flow cytometry, Transwell® and scratch assays, respectively. We exposed ORSCs to kartogenin (1 µM) and determined changes in mRNA and protein levels of transforming growth factor (TGF)-β2/Smad signaling molecules by reverse transcription polymerase chain reaction, western blotting, and immunofluorescence. We also examined the effects of kartogenin (10 µM) on HFs in mice by histology following cutaneous injection. Results: Kartogenin enhanced ORSC proliferation and migration function in a dose-dependent manner, and downregulated the expression of TGF-β2/Smad signaling molecules in vitro. Injection of kartogenin delayed catagen phase and increased regenerated hair length in mice in vivo. Conclusions: Kartogenin modulates HF growth and regulates the hair cycle and the TGF-β2/Smad signaling pathway, providing a potential new approach for the treatment of hair loss.
| S-EPMC8964329 | biostudies-literature
Project description:Trichoderma spp. are ubiquitous soil-borne ascomycetous fungi that have been used widely in the biological control of plant diseases. Certain strains also exhibit growth promotion of plants, but the mechanism for this phenomenon has not yet been elucidated. We have recently identified an isolate of T. hamatum that causes significant increases in the development of Arabidopsis root systems. The aim of this work is to elucidate the mechanism of root growth promotion. One approach is to analyse the transcriptome of plants grown in the presence and absence of the fungus. Experimenter name = Christopher Thornton Experimenter phone = 01392 264653 / 01392 264689 Experimenter department = Washington Singer Lab Experimenter address = School of Biological and Chemical Sciences Experimenter address = University of Exeter Experimenter address = Perry Road, Exeter, Experimenter zip/postal_code = EX4 4QG Experimenter country = UK Keywords: pathogenicity_design, stimulus_or_stress_design
2007-01-08 | GSE5640 | GEO
Project description:BackgroundEndophytic fungi are known plant symbionts. They produce a variety of beneficial metabolites for plant growth and survival, as well as defend their hosts from attack of certain pathogens. Coastal dunes are nutrient deficient and offer harsh, saline environment for the existing flora and fauna. Endophytic fungi may play an important role in plant survival by enhancing nutrient uptake and producing growth-promoting metabolites such as gibberellins and auxins. We screened roots of Ixeris repenes (L.) A. Gray, a common dune plant, for the isolation of gibberellin secreting endophytic fungi.ResultsWe isolated 15 endophytic fungi from the roots of Ixeris repenes and screened them for growth promoting secondary metabolites. The fungal isolate IR-3-3 gave maximum plant growth when applied to waito-c rice and Atriplex gemelinii seedlings. Analysis of the culture filtrate of IR-3-3 showed the presence of physiologically active gibberellins, GA1, GA3, GA4 and GA7 (1.95 ng/ml, 3.83 ng/ml, 6.03 ng/ml and 2.35 ng/ml, respectively) along with other physiologically inactive GA5, GA9, GA12, GA15, GA19, GA20 and, GA24. The plant growth promotion and gibberellin producing capacity of IR-3-3 was much higher than the wild type Gibberella fujikuroi, which was taken as control during present study. GA5, a precursor of bioactive GA3 was reported for the first time in fungi. The fungal isolate IR-3-3 was identified as a new strain of Penicillium citrinum (named as P. citrinum KACC43900) through phylogenetic analysis of 18S rDNA sequence.ConclusionIsolation of new strain of Penicillium citrinum from the sand dune flora is interesting as information on the presence of Pencillium species in coastal sand dunes is limited. The plant growth promoting ability of this fungal strain may help in conservation and revegetation of the rapidly eroding sand dune flora. Penicillium citrinum is already known for producing mycotoxin citrinin and cellulose digesting enzymes like cellulase and endoglucanase, as well as xylulase. Gibberellins producing ability of this fungus and the discovery about the presence of GA5 will open new aspects of research and investigations.
| S-EPMC2631606 | biostudies-literature
Project description:BackgroundAlopecia areata (AA) is the second most frequent nonscarring alopecia after androgenetic alopecia; the trigger factor induces changes in the growth plate of hair bulb and leads to premature termination of anagen phase. Epidermal growth factor (EGF) can be the key molecule that participates in initiation and suppression of normal hair growth cycle. The role of EGF in the pathogenesis of AA is still uncertain.Aim of the workThis aim is to estimate the serum level of EGF in patients with AA trying to detect its role in AA pathogenesis and correlate it with the disease severity.Subjects and methodsThis case-control study included 60 clinically diagnosed patients with AA with different variants and severities and 25 age- and sex-matched healthy controls. EGF level was measured using ELISA.ResultsThe mean serum EGF was statistically significantly higher in patients than of controls (P < 0.0003). The EGF level was higher in patients with disease duration >1 month than patients with disease duration ? 1 month, and it was higher in patients with high recurrence than patients without recurrence (P > 0.05). The EGF in patients of severe AA was statistically significantly higher than moderate AA patients, and moderate cases were higher than mild AA patients (P = 0.0001). Furthermore, the level of EGF with scalp involvement was higher; the highest serum level of EGF marker in S4 (75%-99%) hair loss then S3 (50%-74% hair loss), illustrated in table (4) followed by different percentage of hair loss, difference statistically significant.ConclusionsElevated hair-specific growth factor as EGF is not always a good sign for hair growth and functioning promotor inducing hair recovery, but it may be linked to the pathogenesis of hair disorders as AA.
| S-EPMC7759056 | biostudies-literature
Project description:The fibroblast growth factor (FGF) family has various biological functions, including cell growth, tissue regeneration, embryonic development, metabolism, and angiogenesis. In the case of hair growth, several members of the FGF family, such as FGF1 and FGF2, are involved in hair growth, while FGF5 has the opposite effect. In this study, the regulation of the hair growth cycle by FGF12 was investigated. To observe its effect, the expression of FGF12 was downregulated in mice and outer root sheath (ORS) by siRNA transfection, while FGF12 overexpression was carried out using FGF12 adenovirus. For the results, FGF12 was primarily expressed in ORS cells with a high expression during the anagen phase of hair follicles. Knockdown of FGF12 delayed telogen-to-anagen transition in mice and decreased the hair length in vibrissae hair follicles. It also inhibited the proliferation and migration of ORS cells. On the contrary, FGF12 overexpression increased the migration of ORS cells. FGF12-overexpressed ORS cells induced the telogen-to-anagen transition in the animal model. In addition, FGF12 overexpression regulated the expression of PDGF-CC, MDK, and HB-EGF, and treatment of these factors exhibited hair growth promotion. Altogether, FGF12 promoted hair growth by inducing the anagen phase of hair follicles, suggesting the potential for hair loss therapy.
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Project description:The dynamic localization of endosomal compartments labeled with targeted fluorescent protein tags is routinely followed by time lapse fluorescence microscopy approaches and single particle tracking algorithms. In this way trajectories of individual endosomes can be mapped and linked to physiological processes as cell growth. However, other aspects of dynamic behavior including endosomal interactions are difficult to follow in this manner. Therefore, we characterized the localization and dynamic properties of early and late endosomes throughout the entire course of root hair formation by means of spinning disc time lapse imaging and post-acquisition automated multitracking and quantitative analysis. Our results show differential motile behavior of early and late endosomes and interactions of late endosomes that may be specified to particular root hair domains. Detailed data analysis revealed a particular transient interaction between late endosomes-termed herein as dancing-endosomes-which is not concluding to vesicular fusion. Endosomes preferentially located in the root hair tip interacted as dancing-endosomes and traveled short distances during this interaction. Finally, sizes of early and late endosomes were addressed by means of super-resolution structured illumination microscopy (SIM) to corroborate measurements on the spinning disc. This is a first study providing quantitative microscopic data on dynamic spatio-temporal interactions of endosomes during root hair tip growth.
| S-EPMC4731515 | biostudies-other
Project description:Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life-cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen-to-anagen transition, and HFSC-specific Sirt7 knockout mice (Sirt7f/f ;K15-Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ-dependent proteasomal degradation to terminate Nfatc1-mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7-/- mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.
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