2012 Dec;37(8):909-12. doi: 10.1111/j.1365-2230.2012.04441.x. Epub 2012 Aug 27.
Safety and efficacy analysis of liposomal insulin-like growth factor-1 in a fluid gel formulation for hair-loss treatment in a hamster model.
Castro RF1, Azzalis LA, Feder D, Perazzo FF, Pereira EC, Junqueira VB, Rocha KC, Machado CD, Paschoal FC, Gnann LA, Fonseca FL.
Author information
Abstract
Insulin-like growth factor (IGF)-1 has shown some interesting results in studies examining its use as a hair-loss treatment. IGF-1 works by regulating cellular proliferation and migration during the development of hair follicles. Hepatotoxicity and myelotoxicity were evaluated in hamsters (Mesocricetus auratus) after topical application of the liquid gel vehicle (placebo), 1% IGF-1 or 3% IGF-1. No significant difference in the levels of aspartate aminotransferase or alanine aminotransferase was found between the control and treated groups. ELISA did not shown any increase in the plasma level of IGF-1. A haematopoietic niche was found, but it was not associated with myelotoxicity. Efficacy was determined by dermatoscopy analysis ofhair density and microscopy analysis of hair diameter, with hair found to be thicker and with more rapid growth in the 3% group than in either the 1% group or the control group. These results strongly suggest that liposomal IGF-1 in a liquid gel formulation is a safe and efficient treatment for hair loss.
© The Author(s). CED © 2012 British Association of Dermatologists.
2013 Dec;38(8):904-10. doi: 10.1111/ced.12120.
Ecklonia cava promotes hair growth.
Bak SS1, Ahn BN, Kim JA, Shin SH, Kim JC, Kim MK, Sung YK, Kim SK.
Author information
Abstract
BACKGROUND:
Previous studies have reported the protective effects on skin elasticity of the edible marine seaweed Ecklonia cava, which acts through regulation of both antioxidative and anti-inflammatory responses.
AIM:
We evaluated the effect of E. cava and one of its components, dioxinodehydroeckol, on hair-shaft growth in cultured human hair follicles and onhair growth in mice.
METHODS:
The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to check cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells after treatment with E. cava and its metabolite, dioxinodehydroeckol. Hair-shaft growth was measured using the in vitro hair-follicle organ-culture system, in the presence or absence of E. cava and dioxinodehydroeckol. Anagen induction activity was examined by topical application of E. cava to the dorsal skin of C57BL/6 mice. Insulin-like growth factor (IGF)-1 expression was measured by reverse transcriptase PCR and ELISA.
RESULTS:
The proliferation activity was found to be highest for the ethyl acetate-soluble fraction of E. cava (EAFE) in DPCs and in ORS cells. Treatment with EAFE resulted in elongation of the hair shaft in cultured human hair follicles, and promoted transition of the hair cycle from the telogen to the anagen phase in the dorsal skin of C57BL/6 mice. In addition, EAFE induced an increase in IGF-1 expression in DPCs. Dioxinodehydroeckol, a component of E. cava, induced elongation of the hair shaft, an increase in proliferation of DPCs and ORS cells, and an increase in expression of IGF-1 in DPCs.
CONCLUSIONS:
These results suggest that E. cava containing dioxinodehydroeckol promotes hair growth through stimulation of DPCs and ORS cells.
© 2013 British Association of Dermatologists.
2014 Feb 7;560:7-11. doi: 10.1016/j.neulet.2013.11.062. Epub 2013 Dec 12.
Insulin-like growth factor 1 induces the transcription of Gap43 and Ntn1 during hair cell protection in the neonatal murine cochlea.
Hayashi Y1, Yamamoto N2, Nakagawa T3, Ito J4.
Author information
Abstract
We previously reported that insulin-like growth factor 1 (IGF-1) protects cochlear hair cells against aminoglycosides through activation of the PI3K/Akt and MEK/ERK pathways in supporting cells. In this study, we found that IGF-1 up-regulated the expression levels of Gap43 and Ntn1 as measured using cDNA microarray analysis and qRT-PCR. Using inhibitors of the PI3K/Akt and MEK/ERK pathways, we reveal that both pathways are involved in the up-regulation of Gap43 and Ntn1 expression. Moreover the time window of Gap43 and Ntn1 transcription was limited to within 12h after IGF-1treatment, indicating that downstream gene expression was tightly controlled by IGF-1.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
KEYWORDS:
Adcy7; Cochlea; ERK; Gap43; Growth associated protein 43 (Gap43); IGF-1; Ier5; Insulin-like growth factor 1 (IGF-1); Kitl; MAPK/ERK kinase; MEK; Microarray; Netrin 1 (Ntn1); Ntn1; PI3K; adenylate cyclase 7; extracellular signal-regulated kinase; growth associated protein 43; immediate early response 5; insulin-like growth factor 1; kit ligand; netrin 1; phosphatidylinositol 3-kinase; qRT-PCR; quantitative reverse transcriptase polymerase chain reaction
2013 Sep;56:29-38. doi: 10.1016/j.mcn.2013.03.003. Epub 2013 Mar 17.
Insulin-like growth factor 1 inhibits hair cell apoptosis and promotes the cell cycle of supporting cells by activating different downstream cascades after pharmacological hair cell injury in neonatal mice.
Hayashi Y1, Yamamoto N, Nakagawa T, Ito J.
Author information
Abstract
Sensorineural hearing loss, which is mainly caused by cochlear hair cell damage, is an intractable disease, as cochlear hair cells and supporting cells are unable to proliferate in postnatal mammals. As a novel and potent treatment for sensorineural hearing loss, we have studied IGF-1 and found that it protects cochlear hair cells from the damage caused by noise and ischemic trauma. Through a clinical trial, we have also confirmed that IGF-1is an effective treatment for idiopathic sudden sensorineural hearing loss. In the current study, we attempted to identify the downstream pathways of the IGF-1 signal and the mechanisms by which IGF-1 protects the neonatal mouse cochlear hair cells that have been damaged by neomycin. IGF-1activated both the PI3K/Akt and MEK/ERK pathways to maintain the hair cell numbers in the injured cochlea. The PI3K/Akt pathway specifically protected the cochlear inner hair cells through the inhibition of apoptosis. In contrast, the MEK/ERK pathway induced the cell cycle promotion of Hensen's and Claudius' cells, the supporting cells that are located lateral to the outer hair cells of the cochlea. This cell cycle promotion of the supporting cells resulted in the maintenance of the outer hair cell numbers. These results indicate that IGF-1 is a growth factor that efficiently regulates different mechanisms through different downstream cascades, thereby protecting cochlear hair cells.
Copyright © 2013 Elsevier Inc. All rights reserved.
KEYWORDS:
Apoptosis; Cell cycle promotion; Cochlea; ERK; HC; Hair cell; IGF-1; IHC; Insulin-like growth factor 1; MAPK; MAPK/ERK kinase; MEK; OHC; PI3K; SC; extracellular signal-regulated kinases; hair cell; inner hair cell; insulin like growth factor 1; mitogen-activated protein kinases; outer hair cell; phosphatidylinositol 3-kinase; supporting cell
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J Dermatol. 2013 Dec;40(12):1054-5. doi: 10.1111/1346-8138.12269. Epub 2013 Oct 26.
Induction of insulin-like growth factor-I by cepharanthine from dermal papilla cells: a novel potential pathway forhair growth stimulation.
Inui S1, Itami S.
2011 Oct;21(5):260-7. doi: 10.1016/j.ghir.2011.07.003. Epub 2011 Aug 11.
Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae.
Zhao J1, Harada N, Okajima K.
Author information
Abstract
We demonstrated that insulin-like growth factor-I (IGF-I) production in dermal papillae was increased and hair growth was promoted after sensory neuron stimulation in mice. Although the androgen metabolite dihydrotestosterone (DHT) inhibits hair growth by negatively modulating growth-regulatory effects of dermal papillae, relationship between androgen metabolism and IGF-I production in dermal papillae is not fully understood. We examined whether DHT inhibits IGF-I production by inhibiting sensory neuron stimulation, thereby preventing hair growth in mice. Effect of DHT on sensory neuron stimulation was examined using cultured dorsal root ganglion (DRG) neurons isolated from mice. DHT inhibits calcitonin gene-related peptide (CGRP) release from cultured DRG neurons. The non-steroidal androgen-receptor antagonist flutamide reversed DHT-induced inhibition of CGRP release. Dermal levels of IGF-I and IGF-I mRNA, and the number of IGF-I-positive fibroblasts around hair follicles were increased at 6h after CGRP administration. DHT administration for 3weeks decreased dermal levels of CGRP, IGF-I, and IGF-I mRNA in mice. Immunohistochemical expression of IGF-I and the number of proliferating cells in hair follicles were decreased and hair re-growth was inhibited in animals administered DHT. Co-administration of flutamide and CGRP reversed these changes induced by DHT administration. These observations suggest that DHT may decrease IGF-I production in dermal papillae by inhibiting sensory neuron stimulation through interaction with the androgen receptor, thereby inhibitinghair growth in mice.
Copyright © 2011 Elsevier Ltd. All rights reserved.
2014 Mar;23(3):216-8. doi: 10.1111/exd.12339.
Insulin-like growth factor-1: roles in androgenetic alopecia.
Panchaprateep R1, Asawanonda P.
Author information
Abstract
Of all the cytokines or growth factors that have been postulated to play a role in hair follicle, insulin-like growth factor-1 (IGF-1) is known to be regulated by androgens. However, how IGF-1 is altered in the balding scalp has not yet been investigated. In this study, expressions of IGF-1 and its binding proteins by dermal papilla (DP) cells obtained from balding versus non-balding hair follicles were quantified using growth factor array. DP cells from balding scalp follicles were found to secrete significantly less IGF-1, IGFBP-2 and IGFBP-4 (P < 0.05) than their non-balding counterparts. Our data confirmed that the downregulation of IGF-1 may be one of the important mechanisms contributing to male pattern baldness.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
KEYWORDS:
IGF-1; androgenetic alopecia; hair follicle
2011 Mar;22(3):227-33. doi: 10.1016/j.jnutbio.2010.01.008. Epub 2010 Jun 23.
Dietary isoflavone increases insulin-like growth factor-I production, thereby promoting hair growth in mice.
Zhao J1, Harada N, Kurihara H, Nakagata N, Okajima K.
Author information
Abstract
Sensory neurons release calcitonin gene-related peptide (CGRP) upon activation. We previously demonstrated that CGRP increases insulin-like growth factor-I (IGF-I) production in various tissues of mice including the skin. We demonstrated that isoflavone increases the CGRP synthesis in the dorsal root ganglion (DRG) neurons in rats. Since IGF-I plays a critical role in hair growth, we hypothesized that isoflavones may promote hair growth by increasing the IGF-I production in hair follicles. We examined this hypothesis using wild-type (WT) and CGRP-knockout (CGRP(-/-)) mice. Isoflavone significantly increased the CGRP mRNA levels in DRG neurons isolated from WT mice (P<.01). Administration of isoflavone for 3 weeks increased the dermal levels of CGRP, IGF-I and IGF-I mRNA in WT mice, but not in CGRP(-/-) mice. Isoflavone administration increased the immunohistochemical expression of IGF-I in hair follicle dermal papilla cells in WT mice. Significant enhancements of hair follicle morphogenesis, hairregrowth, and hair pigmentation were also observed in WT mice administered isoflavone. However, none of these effects in WT mice were observed in CGRP(-/-) mice. These observations strongly suggest that isoflavone might increase IGF-I production in the hair follicle dermal papilla cells in mice through increasing CGRP production in the sensory neurons, thereby promoting hair growth associated with melanogenesis in mice.
Copyright © 2011 Elsevier Inc. All rights reserved.
2011;6(12):e28474. doi: 10.1371/journal.pone.0028474. Epub 2011 Dec 2.
Induction of hair growth by insulin-like growth factor-1 in 1,763 MHz radiofrequency-irradiated hair follicle cells.
Yoon SY1, Kim KT, Jo SJ, Cho AR, Jeon SI, Choi HD, Kim KH, Park GS, Pack JK, Kwon OS, Park WY.
Author information
Abstract
Radiofrequency (RF) radiation does not transfer high energy to break the covalent bonds of macromolecules, but these low energy stimuli might be sufficient to induce molecular responses in a specific manner. We monitored the effect of 1,763 MHz RF radiation on cultured human dermal papilla cells (hDPCs) by evaluating changes in the expression of cytokines related to hair growth. The expression of insulin-like growth factor-1 (IGF-1) mRNA in hDPCs was significantly induced upon RF radiation at the specific absorption rate of 10 W/kg, which resulted in increased expression of B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL-2) and cyclin D1 (CCND1) proteins and increased phosphorylation of MAPK1 protein. Exposure to 10 W/kg RF radiation 1 h per day for 7 days significantly enhanced hair shaft elongation in ex vivo hair organ cultures. In RF-exposed follicular matrix keratinocytes in the hair bulb, the expression of Ki-67 was increased, while the signal for terminal deoxynucleotidyl transferase dUTP nick end labeling was reduced. From these results, we suggest that 1,763 MHz RF exposure stimulates hair growth in vitro through the induction of IGF-1 in hDPCs.
2014 Apr-Jun;24(2-3):89-94. doi: 10.1016/j.ghir.2014.03.004. Epub 2014 Mar 30.
Exogenous IGF-1 promotes hair growth by stimulating cell proliferation and down regulating TGF-β1 in C57BL/6 mice in vivo.
Li J1, Yang Z2, Li Z1, Gu L1, Wang Y1, Sung C3.
Author information
Abstract
OBJECTIVE:
Insulin-like growth factor 1 (IGF-1) increases the growth of cultured hair follicles and plays a role in regulating hair migration during the development of hair follicles in transgenic mice. However, the exogenous effect of IGF-1 on hair growth in wild-type mice has not been reported. In the present study, we examined whether IGF-1 was an important regulator of hair follicle growth in wide-type mice in vivo.
DESIGN:
C57BL/6 mice were injected with different concentrations of IGF-1 on dorsal skin. The treated tissues were analyzed by immunoassay methods for TGF-β1 and BrdU.
RESULTS:
Local injection of IGF-1 increased hair follicle number and prolonged the growing phase during the transition from anagen to telogen. Meanwhile, immunology analyses revealed that IGF-1 also stimulated the proliferation of follicle cells in anagen of the matrix and down regulated TGF-β1 expression in hair follicles.
CONCLUSIONS:
These observations suggest that IGF-1 is an effective stimulator of hair follicle development in wide-type mice in vivo and may be a promising drug candidate for baldness therapy.
Copyright © 2014. Published by Elsevier Ltd.
2013 Mar;22(3):168-71. doi: 10.1111/exd.12024. Epub 2012 Sep 28.
Androgen actions on the human hair follicle: perspectives.
Inui S1, Itami S.
Author information
Abstract
Androgens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA). This condition is known as 'androgen paradox'. Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone. In hair follicles, 5α-reductase type 1 and 2, androgen receptors (AR) and AR coactivators can regulate androgen sensitivity of dermal papillae (DP). To regulate hair growth, androgens stimulate production of IGF-1 as positive mediators from beard DP cells and of TGF-β1, TGF-β2, dickkopf1 and IL-6 as negative mediators from balding DP cells. In addition, androgens enhance inducible nitric oxide synthase from occipital DP cells and stem cell factor for positive regulation ofhair growth in beard and negative regulation of balding DP cells. Moreover, AGA involves crosstalk between androgen and Wnt/β-catenin signalling. Finally, recent data on susceptibility genes have provided us with the impetus to investigate the molecular pathogenesis of AGA.
© 2012 John Wiley & Sons A/S.
2013 Dec 31;29(4):241-7. doi: 10.5487/TR.2013.29.4.241.
Action Mechanism of Chamaecyparis obtusa Oil on Hair Growth.
Park YO1, Kim SE2, Kim YC1.
Author information
Abstract
This study was carried out to examine the action mechanism of Chamaecyparis obtusa oil (CO) on hair growth in C57BL/6 mice. For alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT) activities in the skin tissue, at week 4, the 3% minoxidil (MXD) and 3% CO treatment groups showed an ALP activity that was significantly higher by 85% (p < 0.001) and 48% (p < 0.05) and an γ-GT activity that was significantly higher by 294% (p < 0.01) and 254% (p < 0.05) respectively, as compared to the saline (SA) treatment group. For insulin-like growth factor-1 (IGF-1) mRNA expression in the skin tissue, at week 4, the MXD and CO groups showed a significantly higher expression by 204% (p < 0.05) and 426% (p < 0.01) respectively, as compared to the SA group. At week 4, vascular endothelial growth factor (VEGF) expression in the MXD and CO groups showed a significantly higher expression by 74% and 96% (p < 0.05) respectively, however, epidermal growth factor (EGF) expression in the MXD and CO groups showed a significantly lower expression by 66% and 61% (p < 0.05) respectively, as compared to the SA group. Stem cell factor (SCF) expression in the MXD and CO groups was observed by immunohistochemistry as significant in a part of the bulge around the hair follicle and in a part of the basal layer of the epidermis. Taking all the results together, on the basis of effects on ALP and γ-GT activity, and the expression of IGF-1, VEGF and SCF, which are related to the promotion of hair growth, it can be concluded that CO induced a proliferation and division of hair follicle cells and maintained the anagen phase. Because EGF expression was decreased significantly, CO could delay the transition to the catagen phase.
KEYWORDS:
Action mechanism; Anagen phase; C57BL/6 mice; Chamaecyparis obtusa oil; Hair growth
2014 Sep 10;5:208. doi: 10.3389/fphar.2014.00208. eCollection 2014.
Application of insulin-like growth factor-1 in the treatment of inner ear disorders.
Yamamoto N1, Nakagawa T1, Ito J1.
Author information
Abstract
Sensorineural hearing loss (SNHL) is considered an intractable disease, given that hair and supporting cells (HCs and SCs) of the postnatal mammalian cochlea are unable to regenerate. However, with progress in regenerative medicine in the 21st century, several innovative approaches for achieving regeneration of inner ear HCs and SCs have become available. These methods include stem cell transplantation, overexpression of specific genes, and treatment with growth factors. Insulin-like growth factor-1 (IGF-1) is one of the growth factors that are involved in the development of the inner ear. Treatment with IGF-1 maintains HC numbers in the postnatal mammalian cochlea after various types of HC injuries, with activation of two major pathways downstream of IGF-1 signaling. In the aminoglycoside-treated neonatal mouse cochlear explant culture, promotion of the cell-cycle in SCs as well as inhibition of HC apoptosis was observed in the IGF-1-treated group. Activation of downstream molecules was observed in SCs and, in turn, SCs contribute to the maintenance of HC numbers. Using comprehensive analysis of the gene expression, the candidate effector molecules of the IGF-1 signaling pathway in the protection of HCs were identified as Netrin1 and Gap43. Based on these studies, a clinical trial has sought to investigate the effects of IGF-1 on SNHL. Sudden SNHL (SSHL) that was refractory to systemic steroids was treated with IGF-1 in a gelatin hydrogel and the outcome was compared with a historical control of hyperbaric oxygen therapy. The proportion of patients showing hearing improvement was significantly higher in the IGF-1-treatment group at 24 weeks after treatment than in the control group. A randomized clinical trial is ongoing to compare the effect of IGF-1 treatment with that of intra-tympanic steroids for SSHL that is refractory to systemic steroids.
KEYWORDS:
MEK/ERK pathway; Netrin1; PI3K/Akt pathway; apoptosis; cell cycle; clinical trial; sensorineural hearing loss
2013 Jul;10(4):460-72.
IGF-I deficiency and hearing loss: molecular clues and clinical implications.
Varela-Nieto I1, Murillo-Cuesta S, Rodríguez-de la Rosa L, Lassatetta L, Contreras J.
Author information
Abstract
Sensorineural hearing loss is a clinical heterogeneous disorder and a significant health-care problem with tremendous socio-economic impact. According to WHO, "Over 5% of the world's population has disabling hearing loss -328 million adults and 32 million children-". In children, early hearing loss affects language acquisition. Hearing deficits are generally associated with the loss of the sensory "hair" cells and/or neurons caused by primary genetic defects or secondary to environmental factors including infections, noise and ototoxic drugs. Hearing loss cannot be reversed and currently the available treatment is limited to hearing aids and cochlear implants. Studies are being conducted to develop alternative treatments combining both preventive and reparative strategies. Human insulin like growth factor (IGF) I deficiency is a rare disease associated with hearing loss, poor growth rates and mental retardation (ORPHA73272, OMIM608747). Similarly, lgf1-/- mice are dwarfs with poor survival rates and congenital profound sensorineural deafness. IGF-I is known to be a neuroprotective agent that maintains cellular metabolism, activates growth, proliferation and differentiation, and limits cell death. Here we will discuss the basic mechanisms underlying IGF-I actions in the auditory system and their clinical implications to pursue novel treatments to ameliorate hearing loss.
PMID: 23957197 [PubMed - indexed for MEDLINE]
2013 Mar;22(3):168-71. doi: 10.1111/exd.12024. Epub 2012 Sep 28.
Androgen actions on the human hair follicle: perspectives.
Inui S1, Itami S.
Author information
Abstract
Androgens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA). This condition is known as 'androgen paradox'. Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone. In hair follicles, 5α-reductase type 1 and 2, androgen receptors (AR) and AR coactivators can regulate androgen sensitivity of dermal papillae (DP). To regulate hair growth, androgens stimulate production of IGF-1 as positive mediators from beard DP cells and of TGF-β1, TGF-β2, dickkopf1 and IL-6 as negative mediators from balding DP cells. In addition, androgens enhance inducible nitric oxide synthase from occipital DP cells and stem cell factor for positive regulation ofhair growth in beard and negative regulation of balding DP cells. Moreover, AGA involves crosstalk between androgen and Wnt/β-catenin signalling. Finally, recent data on susceptibility genes have provided us with the impetus to investigate the molecular pathogenesis of AGA.
© 2012 John Wiley & Sons A/S.
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