Promote Hair Growth Research Articles

Utilization of response surface design for development and optimization of rosuvastatin calcium-loaded nano-squarticles for hair growth stimulating VEGF and IGF production: in-vitro and in-vivo evaluation

Introduction Countless individuals experience negative emotions as hair loss pattern affects their self-esteem and well-being. Rosuvastatin calcium (Ca-RUV) was reported to stimulate the growth of the hair in the applied area, hence, it was selected as a potential hair loss treatment drug. Significance This study aims to develop and optimize (Ca-RUV) loaded squarticles (SQRs) and assess their ability to deliver and release Ca-RUV in the hair follicle for the promotion of hair growth. Methods A response surface design was utilized to study the effect of varying Pluronic® F68 (PF68) and the percentage of liquid lipids within the core of the SQRs and the effects of particle size, entrapment efficiency, and drug released percentage after 24 h (%Q24) were assessed. The optimized formula was subjected to DSC, XRD, and in-vivo evaluation in rats. Results SQRs stabilized by 0.8% PF68 and contained 37.5% liquid lipids showed an acceptable particle size (250 nm), drug entrapment efficiency (75%), and %Q24 (100%). The in-vivo studies illustrated the ability of the formula to regrow hair in animals after 10 days due to the elevation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) to their normal values and by 9% and 54%, respectively, relative to standard therapy minoxidil (5%). Conclusion Thus, it can be concluded that the optimized formula of Ca-RUV loaded SQRs showed superior in-vivo results in the promotion of hair growth in a shorter period relative to the marketed product. Therefore, the formula can offer a viable option for the treatment of hair loss.

Collagen Hydrolysate from the Scales of Mozambique Tilapia (Oreochromis mossambicus) Improve Hair and Skin Health by Alleviating Oxidative Stress and Inflammation and Promoting Hair Growth and Extracellular Matrix Factors.

Fish-derived collagen hydrolysate (CH) has shown promise in improving hair and skin health. Therefore, this study sought to comprehensively assess the effects of CH extracted from Mozambique tilapia (Oreochromis mossambicus) scales on hair and skin using in vitro and in vivo models. Human dermal papilla cells (hDPCs) were used for antioxidant and gene expression analyses, while C57BL/6 mice were orally administered CH for six weeks to assess hair growth patterns. The mice were divided into four groups: negative control (NC; distilled water), positive control (PC; 1 mg/kg finasteride), CH500 (500 mg/kg BW CH), and CH1000 (1000 mg/kg BW CH). CH mitigated catalase activity reduction in hDPCs, increased IGF-1 and VEGF levels, and decreased TGF-β1, TNF-α, and IL-1β expression. In vivo, CH treatment improved hair growth index, length, diameter, weight, and density. Scanning electron microscopy revealed reduced hair damage. Moreover, CH up-regulated IGF-1, VEGF, Elastin, and HAS2 mRNA expression while down-regulating TNF-α and IL-1β. CH enhanced hair shine, growth, and skin health while alleviating inflammation. These findings demonstrate the potential of CH in alleviating oxidative stress, promoting hair growth, and enhancing skin health, both in vitro and in vivo. Fish-derived CH offers a cost-effective and bioavailable option for improving hair and skin health.

Modulation of hair growth by topical drug delivery enhanced by STAR particles

Topical treatments to modulate hair growth are generally limited by low drug bioavailability due to poor skin permeability. Here, we studied the use of STAR particles, which are millimeter-sized ceramic particles with protruding microneedles, to form micropores in the skin to increase skin permeability to hair growth-modulating drugs. STAR particle design and fabrication were optimized, and the resulting STAR particles were shown to reduce lag time and increase skin permeability to minoxidil and acyclovir by more than three-fold compared to no treatment in pig skin ex vivo. In rats, STAR particles also improved topical delivery of minoxidil and acyclovir, which resulted in an increase or a decrease in the number, length and/or thickness of hairs and/or the number of anagen-phase hair follicles after minoxidil or acyclovir treatment, respectively. Clinical exam and histological evaluation showed no evidence of skin irritation or other adverse effects of the treatments. We conclude that STAR particles can increase topical delivery of minoxidil and acyclovir to improve modulation of hair growth promotion and inhibition, respectively.

Cedrol-loaded dissolvable microneedles based on flexible backing for promoting hair growth

ABSTRACT Objectives The dissolvable microneedles loaded with cedrol based on flexible backing were developed to deliver cedrol directly and continuously to the dermis, where the drug concentration in the hair follicle can be increased locally. Methods The tip-layer matrix solution was prepared by mixing cedrol and polyvinylpyrrolidone K25 (PVP K25), and the pedestal matrix solution was prepared with aqueous hyaluronic acid. The cedrol-loaded dissolvable microneedles (cedrol-DMNs) were prepared under vacuum conditions. The mechanical properties, pig skin penetration efficiency, in vitro cutaneous permeation test, and the amount of drug in the skin and receptor chamber were evaluated. Pharmacodynamical studies were performed with C57BL/6 mice. Results The mechanical properties of cedrol-DMNs were good. In vitro cutaneous permeation tests and pharmacodynamical studies demonstrated that cedrol-DMN could efficiently deliver the drug to the deep dermis and effectively promote hair growth. Conclusions The cedrol-DMNs offer a promising strategy for treating patients suffering from hair loss.

BFNB Enhances Hair Growth in C57BL/6 Mice through the Induction of EGF and FGF7 Factors and the PI3K-AKT-β-Catenin Pathway.

The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured Bacopa procumbens (BFNB) on the promotion of hair growth in C57BL/6 mice. The characterization of the follicular phases and histomorphological analysis showed that the topical application of the formulation for 15 days significantly increased pigmentation and hair growth on the dorsum and head of the mice. Additionally, an acceleration of the follicular cycle phases was observed, along with an increase in the number of follicles, hair length, and diameter, compared to mice treated with minoxidil. In silico analysis and molecular characterization demonstrated that BFNB enhances the expression of epidermal growth factor (EGF) and fibroblast growth factor 7 (FGF7), activating the PI3K-AKT-β-catenin signaling pathway, as well as the expression of PCNA, KI-67, Cyclin D1, and Cyclin E, regulating the cell cycle and cell proliferation, crucial events for hair regeneration. Our results strongly suggest the utility of BFNB as a therapeutic alternative to stimulate hair growth and promote hair health.

The In Vivo and In Vitro Effects of Terminalia bellirica (Gaertn.) Roxb. Fruit Extract on Testosterone-Induced Hair Loss.

Due to the continuous increase in patients with androgenetic alopecia (AGA) and psychological disorders such as depression and anxiety, the demand for hair loss treatment and effective hair growth materials has increased. Terminalia bellirica (Gaertn.) Roxb. (TBE) reportedly exerts anti-inflammatory, hepatoprotective, and antidiabetic effects, among others, but its effects on testosterone (TS)-inhibited hair growth remains unclear. In this study, we evaluated the effects of TBE on TS-induced hair growth regression in human follicle dermal papilla cells (HFDPCs) and C57BL/6 mice. Oral administration of TBE increased TS-induced hair growth retardation. Interestingly, effects were greater when compared with finasteride, a commercial hair loss treatment product. Histological analyses revealed that oral TBE administration increased hair follicles in the dorsal skin of C57BL/6 mice. Additionally, western blotting and immunofluorescence showed that oral TBE administration recovered the TS-induced inhibition of cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki67 expression in vivo. Using in vitro proliferation assays, TBE promoted HFDPC growth, which was suppressed by TS treatment. Thus, TBE may be a promising nutraceutical for hair health as it promoted hair growth in AGA-like in vitro and in vivo models.

Sensitive Quantitative In Vivo Assay for Evaluating the Effects of Biomolecules on Hair Growth and Coloring Using Direct Microinjections into Mouse Whisker Follicles.

Many people suffer from hair loss and abnormal skin pigmentation, highlighting the need for simple assays to support drug discovery research. Current assays have various limitations, such as being in vitro only, not sensitive enough, or unquantifiable. We took advantage of the bilateral symmetry and large size of mouse whisker follicles to develop a novel in vivo assay called "whisker follicle microinjection assay". In this assay, we plucked mouse whiskers and then injected molecules directly into one side of the whisker follicles using microneedles that were a similar size to the whiskers, and we injected solvent on the other side as a control. Once the whiskers grew out again, we quantitatively measured their length and color intensity to evaluate the effects of the molecules on hair growth and coloring. Several chemicals and proteins were used to test this assay. The chemicals minoxidil and ruxolitinib, as well as the protein RSPO1, promoted hair growth. The effect of the clinical drug minoxidil could be detected at a concentration as low as 0.001%. The chemical deoxyarbutin inhibited melanin production. The protein Nbl1 was identified as a novel hair-growth inhibitor. In conclusion, we successfully established a sensitive and quantitative in vivo assay to evaluate the effects of chemicals and proteins on hair growth and coloring and identified a novel regulator by using this assay. This whisker follicle microinjection assay will be useful when investigating protein functions and when developing drugs to treat hair loss and abnormal skin pigmentation.

<i>Alpinia zerumbet</i>: A Review of the Chemistry, Quantity, and Pharmacological Properties of Selected Kavalactones

Alpinia zerumbet or shell ginger is a ginger plant with diverse chemical constituents and medicinal and non-medicinal uses. Dihydro-5,6-dehydrokawain (DDK) and Dehydrokawain (DK) are two kavalactones (also known as kava pyrones or styrylpyrones) from A. zerumbet. Both DDK and DK have a carbonyl group at C2, a methoxy group at C4, and a double bond at C5 and C6. DK has a double bond at C7 and C8 that is absent in DDK. Quantity of DDK in A. zerumbet can be ranked as rhizome > leaf > flower > stem > seed. The pericarp and seed placenta of the fruit has higher quantity of DDK than the leaf. In most plant parts, the contents of DDK are higher than those of DK. Hispidin (HP) is synthesized from DK by hydrolysis. These three kavalactones from A. zerumbet have the most promising pharmacological properties that include insecticidal, fungicidal, antioxidant, inhibition of enzymes, inhibition of Advanced Glycation End-products (AGEs), inhibition of p21-activated kinase 1 (PAK1), inhibition of LIM domain kinase 1 (LIMK1), promotion of hair growth, anti-cancer, inhibition of melanogenesis, anti-inflammatory, anti-obesity, HIV-1 integrase inhibition, neuraminidase inhibition, osteogenic, anti-platelet aggregation, cytoprotective, anti-ulcerative, and singlet oxygen quenching activities. Some fields for further research are suggested. Sources of information in this review were from Google, Google Scholar, Science Direct, PubMed, J-Stage, China National Knowledge Infrastructure (CNKI), and PubChem.

Mesenchymal stromal cell–derived magnetic nanovesicles for enhanced skin retention and hair follicle growth

Background aimsExtracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications. MethodsIn this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle–incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field. ResultsFollowing the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and β-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis. ConclusionsThe proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.

Does an apple a day keep away diseases? Evidence and mechanism of action.

Apples and their products exemplify the recently reemphasized link between dietary fruit intake and the alleviation of human disease. Their consumption does indeed improve human health due to their high phytochemical content. To identify potentially relevant articles from clinical trials, some epidemiological studies and meta-analyses, and in vitro and in vivo studies (cell cultures and animal models), PubMed was searched from January 1, 2012, to May 15, 2022. This review summarized the potential effects of apple and apple products (juices, puree, pomace, dried apples, extracts rich in apple bioactives and single apple bioactives) on health. Apples and apple products have protective effects against cardiovascular diseases, cancer, as well as mild cognitive impairment and promote hair growth, healing of burn wounds, improve the oral environment, prevent niacin-induced skin flushing, promote the relief of UV-induced skin pigmentation, and improve the symptoms of atopic dermatitis as well as cedar hay fever among others. These effects are associated with various mechanisms, such as vascular endothelial protection, blood lipids lowering, anti-inflammatory, antioxidant, antiapoptotic, anti-invasion, and antimetastatic effects. Meanwhile, it has provided an important reference for the application and development of medicine, nutrition, and other fields.

A Clinical Trial of Treating Androgenic Alopecia with Mesenchymal Stem Cell Suspension Derived from Autologous Hair Follicle.

Androgenic alopecia (AGA) is characterized by progressive hair follicle miniaturization. Novel treatments are needed to intervene in the miniaturization process. The authors aimed to evaluate the efficacy, safety, effectiveness, and effective population of autologous hair follicle mesenchymal stem cell therapy for the treatment of advanced AGA in Chinese individuals. Fifty patients ranging in age from 25 to 45 years (average, 32 ± 1.24 years) were included. None of them had ever used minoxidil, finasteride, or other drugs to promote hair growth. Healthy hair follicles were extracted from the occipital area and treated to obtain hair follicle mesenchymal stem cell suspensions. The recipient sites were divided into 2 groups. Nine points were injected in a 1-cm 2 area, and 100 µL of solution containing either 1 × 10 5 cells or normal saline was injected at each point. The follow-up duration was 9 months. Observers were blinded to patient groupings and measurements. An increased proportion of terminal hair and hair shaft diameter was observed in the experimental group at 1 month. The effect lasted for 3 months. The hair-thickening effect of advanced miniaturized hair follicles with hair shaft diameter less than 60 µm was more notable than that for above 60 µm. No patient experienced any obvious side effects. Hair follicle mesenchymal stem cells were effective in the treatment of advanced AGA in Chinese individuals. A hair shaft diameter of 60 µm can be used as a key index to predict the effectiveness of the therapy. Therapeutic, II.

Hair Growth Effect of DN106212 in C57BL/6 Mouse and Its Network Pharmacological Mechanism of Action.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.

Ginsenoside CK inhibits androgenetic alopecia by regulating Wnt/β‐catenin and p53 signaling pathways in AGA mice

AbstractAndrogenetic alopecia (AGA) is one of the most common chronic skin diseases caused by the destruction of androgens in the body. It is caused by the excessive deposition of dihydrotestosterone around the hair follicle, resulting in hair follicle atrophy and hair cell apoptosis. It causes great anxiety and psychological distress to patients and affects sexual function in severe cases. As traditional Chinese herbs, ginsenosides have been proven to possess various pharmacological activities. Ginsenoside CK is one of the main ginsenosides, but its role and molecular mechanism in treating AGA remain unclear. Here, we found that ginsenoside CK intervention significantly reduced back hair loss in AGA mice, improved sexual organ damage and hair follicle cell apoptosis, and promoted hair growth in AGA mice. Ginsenoside CK treatment inhibited p53 expression, reduced the apoptosis of hair follicle cells induced by hormone deposition, activated the Wnt/β‐catenin cell proliferation signaling pathway, increased the level of vascular endothelial growth factor, promoted cell proliferation, and improved the atrophy of hair follicle tissue. Ginsenoside CK treatment also reduced testosterone levels in AGA mice, improved testicular tissue inflammation, and restored normal hormone metabolism in AGA mice. Our results indicated that ginsenoside CK reduced hair follicle cell apoptosis, promoted proliferation and development, and prolonged the hair growth cycle by regulating the Wnt and p53 signaling pathways, indicating the potential value of ginsenoside CK as a natural therapeutic agent for AGA.

Pharmacological activities of Eclipta alba (L.) Hassk. (Bhringaraja): A Review

Eclipta alba (L.) Hassk, family: Asteraceae (Bhringaraja) is traditionally used in medicaments in Asian countries including Sri Lanka. Pharmaceutical products containing Eclipta alba (E.alba) have been used for different kinds of diseases and it had been mentioned in different types of prescriptions in Authentic texts in Ayurveda (Samhitha Grantha). Objective of this review is to discuss about the pharmacological activities and provides an integrated, synthesized overview of the current state of knowledge on E. alba with Ayurvedic and traditional knowledge. Data collected from Ayurveda texts, research papers, peer-reviewed indexed scientific journals, and authentic websites. E. alba is a small branched perennial herb, found in sandy and clay soils as waterlogged areas. E. alba has hepatoprotective, hair growth promoting, antidiabetic, analgesic, anti-inflammatory, neuropharmacological, antioxidant, antimicrobial, cardiovascular, immunomodulatory, anti-epilepsy, anti-venom, anticancer, antiulcer, anthelmintic, and anti-hyperlipidemic properties. The reason for these properties is stated to be its major chemical compounds such as wedelolactone, dimethyl wedeloctone, ecliptic, etc. Therapeutic actions such as relieving swelling (Sothahara), relieving pains (Vedana Sthapana), purifying wounds (Vrana shodhana), wound healing (Vrana ropaṇa), giving normal colour to body parts (Sa-varṇakaraṇa), improving vision (Chakshushya), promoting hair growth (Keshavardhana), giving normal black to hair (Kesha ranjana) etc. have been mentioned in Samhitha Grantha and Ayurveda pharmacopeia.

The Role of EAAT4 in Epidermal Differentiation and Calcium Homeostasis During Aging

The Role of EAAT4 in Epidermal Differentiation and Calcium Homeostasis During Aging

DKK1-targeting cholesterol-modified siRNA implication in hair growth regulation

Despite advancements in medical research, androgenetic alopecia (AGA) remains a humankind problem that still needs to be overcome. To date, clinical practice lacks an ideal treatment for AGA. The Wnt/β-catenin signaling pathway is evidenced to play a key role in hair regrowth, hence, modulating this signaling pathway for AGA therapy appears to be rational. One of the major inhibitors of the canonical Wnt/β-catenin signaling pathway is dickkopf-related protein 1 (DKK1). In this report, we have selected a small interfering RNA (siRNA) targeting DKK1 in vitro via qPCR and then tested its efficacy in vivo on the depilated dorsal skin of the mice. The changes in hair growth in different groups were observed over time. Moreover, the visual observation of the hair growth and hematoxylin and eosin (HE) staining showed that DKK1-targeting siRNA reveals non-inferior results compared with the mice treated with the Food and Drug Administration (FDA)-approved, commercially available minoxidil (5%) topical solution that was used as a positive control. Both– positive control and DKK1-targeting siRNA groups demonstrated significantly superior results compared with the control group that received negative control siRNA. Consequently, siRNAs targeting DKK1 may promote hair growth regulation in the AGA population via potentially activating the Wnt/β-catenin signaling pathway.

Millet seed oil activates β-catenin signaling and promotes hair growth.

Alopecia, regardless of gender, exacerbates psychological stress in those affected. The rising prevalence of alopecia has fueled a research interest in preventing hair loss. This study investigates the potential of millet seed oil (MSO) in promoting the proliferation of hair follicle dermal papilla cells (HFDPC) and stimulating hair growth in animals with testosterone-dependent hair growth inhibition as part of a study on dietary treatments to improve hair growth. MSO-treated HFDPC significantly increased cell proliferation and phosphorylation of AKT, S6K1, and GSK3β proteins. This induces β-catenin, a downstream transcription factor, to translocate to the nucleus and increase the expression of factors related to cell growth. In a C57BL/6 mice model in which hair growth was inhibited by subcutaneous testosterone injection after shaving the dorsal skin, oral administration of MSO stimulated hair growth in the subject mice by increasing the size and number of hair follicles. These results suggest that MSO is a potent agent that may help prevent or treat androgenetic alopecia by promoting hair growth.

Dietary marine-derived ingredients for stimulating hair cell cycle

In normal condition human hair growth occurs through three phases, anagen (growth phase included about 85 % of hairs, last from 2 to 6 years), catagen (transitional phase lasting up to 2 weeks) and telogen (resting phase which last from 1 to 4 months). Natural dynamics of the hair growth process can be impaired by several factors, such as genetic predisposition, hormonal disorders, aging, poor nutrition or stress, which can lead to the slowdown in the growth of hair or even hair loss. The aim of the study was to assess the hair growth promotion effect of marine-derived ingredients, hair supplement Viviscal® and its raw components (marine protein complex AminoMarC®, shark and oyster extract). Cytotoxicity, production of alkaline phosphatase and glycosaminoglycans, as well as expression of genes involved in hair cycle-related pathways were investigated using dermal papilla cells, both immortalized and primary cell lines. Tested marine compounds showed no evidence of cytotoxicity under in vitro conditions. Viviscal® significantly increased proliferation of dermal papilla cells. Moreover, tested samples stimulated cells to produce alkaline phosphatase and glycosaminoglycans. Increased expression of hair cell cycle-related genes was also observed. The obtained results indicate that marine-derived ingredients stimulate hair growth through anagen activation.

Promotion of hair growth by Lactobacillus and fermented traditional Korean berry in C57BL/6 mice

Hair loss is the state of losing hair from the scalp or entire body when new hair does not replace the hair that has fallen out. Currently, remedies such as oral finasteride and topical minoxidil are commonly used. However, these drugs may have temporary effects and cause side effects such as depression, irregular heartbeat and weight gain when used long term. Therefore, an alternative hair growth promoting agent is needed. The hair follicle undergoes anagen, catagen, and telogen phase which affect hair growth, and this hair-growth cycle is regulated by growth factors, cytokines, and hormones. Some studies reported that the gut microbiome (GM) regulates the transition between the hair growth cycle by producing hair growth-related factors and nutrients. Also, inflammation by GM affects the cascade of the inflammation in the hair follicle, which may lead to hair growth arrest. Previous studies showed strains of Lactobacillus (LAB) have anti-oxidative and anti-inflammatory effects in an HT-29 human colon epithelial cell model and an HaCaT human keratinocyte cell model. Also, traditional Korean berry has anti-inflammatory effects in an HT-29 model. Thus, LAB and fermented traditional Korean berry by LAB (FB) may promote hair growth by regulating gut microbiome. This study investigated the effect of LAB and FB on hair growth in vivo. Six-week-old male C57BL/6 mice were used for evaluating the hair growth-promoting effects of the LAB and FB. The dorsal hair of mice was depilated, and they were orally treated with LAB at 1010 CFU/kg and FB at 250mg/kg daily for 22 days. As a result, the hair re-growth rate was significantly increased in LAB and FB groups compared with the control group. In the histological analysis of skin, FB increased the number of hair follicle and subcutaneous fat layer thickness. The mRNA expression levels of hair growth-related growth factors such as VEGF and IGF-1 are significantly increased in colon and skin. Moreover, Treatment of LAB and FB changed the composition of the microbiome and short chain fatty acids in mice. Altogether, LAB and FB supplementation may promote hair growth by regulating growth factors and altering gut microbiota compositions. In conclusion, strain of LAB and FB are potential novel approaches for hair growth promotion. This work was supported by Korea Testing Laboratory This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Injury-induced hair growth response is promoted by tissue macrophages via insulin-like growth factor 1

Abstract Hair follicles (HFs) produce hair to mediate the first line of defense in mammals. HFs undergo cyclical production of hair (anagen), and while this process is unsynchronized during adulthood, external cues, including shaving, induce synchronized anagen and bolster the surface barrier. Herein, we show that macrophages were crucial in promoting anagen. Shaving triggered the accumulation of macrophages to the secondary hair germs (SHG), which underwent proliferation as early as Day3 post-induction. Constitutive ablation of macrophages markedly delayed anagen, and targeted ablation of macrophages at Day 3, but not at Day 0 or Day 6 post-shaving, impaired SHG activation with delayed anagen. Anagen entry was dependent on Folr2 +tissue macrophages, but not on CCR2 +monocyte-derived macrophages. Single-cell RNA-sequencing and cell-cell communication analyses revealed that Folr2 +macrophages communicated with the SHGs via Igf1 (encoding insulin-like growth factor 1 or IGF1). Ablation of macrophages and deletion of IGF1 from macrophages decreased AKT signaling in SHG and led to delayed anagen, both which were rescued via injection of recombinant IGF1 in vivo. Single-cell ATAC-sequencing revealed that the lack of IGF1-from macrophages resulted in alteration of transcription factor motif enrichment and decreased chromatin accessibility in various genes in SHGs, demonstrating that macrophages primed the SHGs to enter anagen by promoting IGF1R signaling. These results highlight the importance of immune-tissue crosstalk in facilitating hair growth and provide impetus for strategies to promote hair growth.