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I know there are a few people here that like to indulge in the pathophysiology/biochemistry of hair loss.
I found the following on another site. Apparently it's from a journal that compiles all this information, but I honeslty can't find the reference. All the appropriate references should be there.
UPREGULATED EXPRESSION
ADRB1 (adrenergic, ß-1-receptor) (HUMAN) (Mouse)
ADRB1 blockade impairs cutaneous wound healing Ohyama et al. (2006)
Adrb1 expression in murine bulge cells in early (anagen). Murine hair cycle modulation by adrenergic agents Botchkarev et al. (1999), Peters et al. (1999) and Souza et al. (2006)
ANGPTL2 (angiopoietin-like) (HUMAN)
Mesenchymal stem cells enhance wound healing through angiopoietin-like triggered differentiation and angiogenesis Ohyama et al. (2006)
Angiopoietins have been identified as the major ligands of the endothelial-specific receptor Tie2. Thus, the Tie2/angiopoietin-like signaling pathway plays a critical role in maintaining HFeSC in the quiescent state in the niche Kuroda et al. (2001), Mecklenburg et al. (2000), Oike et al. (2004), Suda et al. (2005), Yano et al. (2001) and Yano et al. (2003)
BMP6 (bone morphogenetic protein) (HUMAN) (Mouse)
BMPs are a family of secreted signaling molecules that can induce ectopic bone growth. Many BMPs are part of the transforming growth factor-ß (TGFß) superfamily Blanpain et al. (2004)
BMP signaling inhibits HF anagen induction by restricting HFeSC/TA activation and expansion. 17-ß-estradiol activates via BMP signaling PI3K/AKT pathways which augment proliferation of HFeSCs/TAs by loss of the quiescent niche Kobielak et al. (2007), Murayama et al. (2007), Ohnemus et al. (2005), Ohnemus et al. (2006) and Zhang et al. (2006)
CALM2 (calmodulin 2 phosphorylase kinase, delta) (HUMAN)
CALM2 functions include roles in growth and the cell cycle as well as in signal transduction and the synthesis and release of neurotransmitters Ohyama et al. (2006)
Calmodulin stimulation activates the expression of ADRB1 and activates therefore signaling pathways which modulate epithelial-mesenchymal transformation. Calmodulin binds additionally the erythropoietin receptor which modulates together with TGFß telomerase activity which could play an important role in HFeSC quiescence Bodó et al. (2007), Lenoir et al. (1986), Prade-Houdellier et al. (2007), Siegl-Cachedenier et al. (2007), Sterin-Borda et al. (2007)
Cdkn1B (cyclin-dependent kinase inhibitor) (Mouse)
Cyclin-dependent kinase inhibitors, like Cdkn1B, are expressed site- and hair cycle-dependently in rat HFs. Involved in the differentiation of follicular epithelial cells Blanpain et al. (2004)
Activation of Bmp signaling induces growth arrest, Cdkn1B expression and plays an important role in regulating cell by modulating the expression of cell -cycle-associated genes in hair matrix keratinocytes. Somatostatin analogues stimulate Cdkn1B expression and inhibit the MAP kinase pathway. Somatostatin itself is an regulator of the HF bulge immunoprivilege (HFeSC niche) Mitsui et al. (2001), Nanba et al. (2003), Niederkorn (2003) and Sharov et al. (2006)
CtgF (connective tissue growth factor) (Mouse)
Involved in inductive properties of fibroblasts during embryogenesis and in adult wound healing, tissue repair and fibrogenesis Blanpain et al. (2004)
Relevant for HFeSC/TA communication with the CTS, e.g. with CTS component of the bulge SC niche? Friedrichsen et al. (2005) and Kennedy et al. (2007)
EDNRB (endothelin receptor B) (HUMAN)
EDNRB appears essential for the continued survival of migrating melanocytes Ohyama et al. (2006)
SOX10 interacts with EDNRB which regulates melanocyte SCs. Binding of Tenascin-C to EDNRB may regulate HFeSC niche properties Boissy and Nordlund (1997), Lange et al. (2007), Slominski et al. (2005) and Yoshida et al. (1996)
ESR1 (estrogen receptor ß) (HUMAN)
The estrogen receptor (ESR) is a ligand-activated transcription factor composed of a and ß domain. These receptors display different immunohistochemical localizations in human scalp skin, where ESRß is predominantly expressed, suggesting their different functional roles in cutaneous biology Ohyama et al. (2006)
17-ß-estradiol activates via the ESR jagged1- and notch1 expression. Jagged1 regulates HF differentiation (HFeSC/TA activation), whereas notch signaling is required for the maintenance of melanocyte SCs in the HFAmbler and Watt (2007), Kwon et al. (2004), Nishikawa and Osawa (2007), Soares et al. (2004), Thornton et al. (2003) and Yoo et al. (2007)
FS (follistatin) (HUMAN)
FS is a gonadal protein that inhibits follicle -stimulating hormone release Ohyama et al. (2006)
FS antagonizes the functions of BMPs and activin. Both mediate interactions between the mesenchymal SC and HFeSC within the niche and form an integrated network Hwang et al. (2005), Nakamura et al. (2003) and Thesleff et al. (2007)
GHR (growth hormone receptor) (HUMAN)
Binding of growth hormone (GH) to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. In transgenic rats in which the GH expression is suppressed the hair enters a long-lasting telogen phase Ohyama et al. (2006)
HF bulge cells which express GHR also express prolactin receptors. These two factors play an important role for the immunocompetent bulge region (HFeSC niche)Dardenne et al. (1998) and Umeda-Ikawa et al. (2006)
GR (Nr3c1; glucocorticoid receptor) (Mouse)
Keratinocytes from both the HF bulge and interfollicular epidermis of mice express Nr3c1Ohyama et al. (2006)
GR signaling has an important role in the homeostasis of HFeSC, and they are more sensitive to the antiproliferative effect of glucocorticoids implicating that the reduction in their number may underlie the tumor suppressor effect of Nr3c1 in the skin Chebotaev et al. (2007) and Morris (2007)
Igfbp-3, -5, -6 (insulin-like growth factor binding proteins 3, 5, 6) (Mouse)
Igfbp-3 inhibits hair matrix keratinocyte proliferation, possibly involved in catagen induction. Igfbp-5 involved in hair shaft formation. Igfbp-6 promotes ß-catenin transcriptional activity Blanpain et al. (2004) and Morris et al. (2004)
Igf-1 production stimulated by major hair growth-regulatory hormones, e.g. insulin, prolactin; main effect likely on TA and their more differentiated progeny. Key role of ß-catenin in HFeSC commitment to HF-type differentiation Alonso and Fuchs (2006), Amini Nik et al. (2007), Paus and Foitzik (2004), Paus et al. (2005), (Schlake, 2005a) and (Schlake, 2005b), Stenn and Paus (2001) and Weger and Schlake (2005)
LTBP1 (latent transforming growth factor ß binding protein 1) (HUMAN) (Mouse)
LTBP1 targets latent complexes of TGFß to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. LTBP1 interacts with fibrillin and is a microfibril-associated protein Blanpain et al. (2004) and Ohyama et al. (2006)
TGFß1/2 are catagen-inducing growth factors. TGFß2 is an inducer of HF morphogenesis. Epidermal growth factor stimulated TGFß1 expression in stromal cells, whereas keratinocyte growth factor stimulated TGFß2 in epithelial cells (mobilization and inactivation of HFeSC) (Foitzik et al., 1999) and (Foitzik et al., 2000), Isogai et al. (2003), Itoh et al. (1998), Paus and Foitzik (2004)
Mmp-2 (matrix metallopeptidase) (Mouse)
The Mmp famliy control extracellular matrix remodelling, including during HF cyclingBlanpain et al. (2004)
Expression of Mmp-2 is increased by thymosinß4. Thymosinß4 accelerates hair growth due to its effect on the active phase of the HF cycle. Activation of EGF receptor by the release of Gprc-ligands through proteolytic action of matrix Mmp´s promotes proliferation, survival, differentiation and migration of HFeSC/TA due to remodelling the basement membrane of the HFeSC-niche Karelina et al. (2000), (Paus et al., 1994a) and (Paus et al., 1994b), Philp et al. (2004) and Shah and Catt, 2004
DOWN REGULATED EXPRESSION
ANGPTL7 (angiopoietin-like 7) (HUMAN)
ANGPTL7 is expressed at high levels in the avascular corneal stromal layer suggested that the protein, similar to certain angiopoietins, acts as a negative regulator of angiogenesisOhyama et al. (2006)
Angiopoietins have been identified as the major ligands of the endothelial-specific receptor Tie2. Thus, the Tie2/Angiopoietin-like signaling pathway plays a critical role in maintaining HFeSC in the quiescent state in the niche Kuroda et al. (2001), Mecklenburg et al. (2000), Peek et al. (2002), Suda et al. (2005) and (Yano et al., 2001) and (Yano et al., 2003)
Cyclin G2 (Mouse)
Estradiol represses expression of the cyclin G2 gene, which encodes a negative regulator of the cell cycle Morris et al. (2004)Cyclin G2 may contribute in maintaining the quiescent state of progenitor and/or differentiated cells. Stossi et al. (2006)
Ir1 (interleukin 1 receptor) (Mouse)
The IL-1 system plays a key role in skin physiology and pathology Morris et al. (2004)
Ir1 plays a role in initiation and maintenance of inflammatory reactions of the immune privileged HFeSC niche McGirt and Beck (2006), Palmer et al. (2007) and Schiller et al. (2006)
LTBP2 (latent transforming growth factor ß binding protein) (HUMAN)
It has thus been suggested that LTBP2 may have multiple functions: as a member of the TGF-ß latent complex, as a structural component of microfibrils, and a role in cell adhesion Ohyama et al. (2006)
LTBP2 has a regulatory mechanism of elastic fiber assembly in which LTBP-2 regulates targeting of DANCE on microfibrils to form elastic fibers and this could be a prerequisite for the HFeSC niche Hirai et al. (2007)
Ntf3 (neurotrophin-3) (Mouse)
Ntf3 and its receptor tyrosine kinase C are essential for nervous system development. Both are expressed in human scalp skin and HFs and exert many growth-regulatory functions beyond the nervous system Morris et al. (2004)
Neurotrophins, including NGF, BDNF, NT-3, and NT-4, and their cognate receptors, tyrosine kinase A-C and p75 neurotrophin receptor exhibit significant, hair cycle-dependent fluctuations on the gene and protein level. Related with a loss of quiescence in the HFeSC-niche by modulating the surrounding neural network Adly et al. (2005) and Botchkarev et al. (2004)
PTGER4 (prostaglandin E receptor) (HUMAN)
Knockout studies in mice suggest that PTGER4 may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses Ohyama et al. (2006)
Prostanoid pathway in HF may regulate hair regrowth. Local production of prostaglandin in stem cell compartments controls injury-induced HFeSC proliferation Colombe et al. (2008), Colombe et al. (2007), Kabashima et al. (2003) and Rakoff-Nahoum and Medzhitov (2007)
OTHERS EXPRESSED IN BULGE REGION.
ADM (adrenomedullin) (HUMAN)
ADM is a potent vasodilator, but also exerts other functions, such as regulating cell growth and antimicrobial defence Müller et al. (2003)
Expression of ADM especially in proximity to the bulge region displaying immune privilege (quiescent HFeSC niche conditions) Müller et al. (2003)
Cald1 (caldesmon-1) (Mouse)
Cald1 was present during the early anagen phases within the bulge and is involved in cytoskeleton remodeling processes which could inhibit HF growth Wollina et al. (1995)
Cald1 modulates the actin cytoskeleton in the bulge region and could be therefore a regulator of the HFeSC-niche Greenberg et al. (2008), Hayashi et al. (2002) and Wollina et al. (1995)
CCND1 (cyclin D1) (HUMAN) (Mouse)
CCND1 forms a complex with and functions as a regulatory subunit of the cyclin-dependent kinases-4 or -6, whose activity is required for cell cycle G1/S transition Xu et al. (2003) and Blanpain et al. (2004)
Localized to suprabasal cells of telogen bulge and anagen ORS. Mediate proliferation HFeSCto differentiated TA cells in the suprabasal ORS. NF-kappaB activation is essential for induction of cyclin D1 and SHH expression and hair placode down growth Schmidt-Ullrich et al. (2006) and Xu et al. (2003)
EPO (erythropoietin) (HUMAN)
HFs express EPO and transcripts for EPO-receptor and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1a Bodó et al. (2007) TGFß blocks EPO signaling downstream of c-myc induction through a SMAD3-dependent mechanism Bodó et al. (2007)
HSD17B4 (hydroxysteroid (17-ß) dehydrogenase 4; 17-ß-estradiol) (HUMAN)
It has long been known that estrogens also profoundly alter HF growth and cycling by binding to locally expressed high-affinity estrogen receptors (ESRs) Ohnemus et al. (2006)
Estrogen arrests murine pelage HFs in telogen and demonstrate that it is a potent inducer of premature catagen development. 17-ß-estradiol activates via the ESR JAGGED1- and NOTCH1 expression. JAGGED1 regulates HF differentiation (HFeSC/TA activation) Ambler and Watt (2007), Nishikawa and Osawa (2007), Ohnemus et al. (2005) and Yoo et al. (2007)
NGF-R (nerve growth factor receptor) (HUMAN)
Expression of NGF-R in the bulge region of plucked human HFsMoll (1996)
NGF-R regulates the immune privilege of the HF which is linked to a HFeSC niche(Peters et al., 2006b) and (Peters et al., 2007)
Substance P (HUMAN) (Mouse)
Substance P down-regulates immunoreactivity for the growth-promoting NGF receptor, whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR) Peters et al. (2007)
TMSB4 (thymosin ß4) (HUMAN) (Mouse) Philp et al. (2004)
TMSB4 up-regulates MMP2 and promotes the migration of HFeSCs/TAs to the base of the HF Karelina et al. (2000), Paus et al., 1994a
Vipr1 (vasoactive intestinal peptide (Vip) receptor 1) (Mouse)
It was demonstrated that Vipr1 is expressed sequentially in the bulge area and the IRS as well as in the sebaceous gland epitheliumWollina et al. (1995)
Vipr1 is expressed in the bulge region during anagen V, but is absent during cycle phases. This suggests a physiological function of Vipr1 in terminating the HF growth during anagen I to IV. Additionally Vip could be a regulator for the immunoprivileged bulge (HFeSC-niche)Luger (2002) and Wollina et al. (1995)
I found the following on another site. Apparently it's from a journal that compiles all this information, but I honeslty can't find the reference. All the appropriate references should be there.
UPREGULATED EXPRESSION
ADRB1 (adrenergic, ß-1-receptor) (HUMAN) (Mouse)
ADRB1 blockade impairs cutaneous wound healing Ohyama et al. (2006)
Adrb1 expression in murine bulge cells in early (anagen). Murine hair cycle modulation by adrenergic agents Botchkarev et al. (1999), Peters et al. (1999) and Souza et al. (2006)
ANGPTL2 (angiopoietin-like) (HUMAN)
Mesenchymal stem cells enhance wound healing through angiopoietin-like triggered differentiation and angiogenesis Ohyama et al. (2006)
Angiopoietins have been identified as the major ligands of the endothelial-specific receptor Tie2. Thus, the Tie2/angiopoietin-like signaling pathway plays a critical role in maintaining HFeSC in the quiescent state in the niche Kuroda et al. (2001), Mecklenburg et al. (2000), Oike et al. (2004), Suda et al. (2005), Yano et al. (2001) and Yano et al. (2003)
BMP6 (bone morphogenetic protein) (HUMAN) (Mouse)
BMPs are a family of secreted signaling molecules that can induce ectopic bone growth. Many BMPs are part of the transforming growth factor-ß (TGFß) superfamily Blanpain et al. (2004)
BMP signaling inhibits HF anagen induction by restricting HFeSC/TA activation and expansion. 17-ß-estradiol activates via BMP signaling PI3K/AKT pathways which augment proliferation of HFeSCs/TAs by loss of the quiescent niche Kobielak et al. (2007), Murayama et al. (2007), Ohnemus et al. (2005), Ohnemus et al. (2006) and Zhang et al. (2006)
CALM2 (calmodulin 2 phosphorylase kinase, delta) (HUMAN)
CALM2 functions include roles in growth and the cell cycle as well as in signal transduction and the synthesis and release of neurotransmitters Ohyama et al. (2006)
Calmodulin stimulation activates the expression of ADRB1 and activates therefore signaling pathways which modulate epithelial-mesenchymal transformation. Calmodulin binds additionally the erythropoietin receptor which modulates together with TGFß telomerase activity which could play an important role in HFeSC quiescence Bodó et al. (2007), Lenoir et al. (1986), Prade-Houdellier et al. (2007), Siegl-Cachedenier et al. (2007), Sterin-Borda et al. (2007)
Cdkn1B (cyclin-dependent kinase inhibitor) (Mouse)
Cyclin-dependent kinase inhibitors, like Cdkn1B, are expressed site- and hair cycle-dependently in rat HFs. Involved in the differentiation of follicular epithelial cells Blanpain et al. (2004)
Activation of Bmp signaling induces growth arrest, Cdkn1B expression and plays an important role in regulating cell by modulating the expression of cell -cycle-associated genes in hair matrix keratinocytes. Somatostatin analogues stimulate Cdkn1B expression and inhibit the MAP kinase pathway. Somatostatin itself is an regulator of the HF bulge immunoprivilege (HFeSC niche) Mitsui et al. (2001), Nanba et al. (2003), Niederkorn (2003) and Sharov et al. (2006)
CtgF (connective tissue growth factor) (Mouse)
Involved in inductive properties of fibroblasts during embryogenesis and in adult wound healing, tissue repair and fibrogenesis Blanpain et al. (2004)
Relevant for HFeSC/TA communication with the CTS, e.g. with CTS component of the bulge SC niche? Friedrichsen et al. (2005) and Kennedy et al. (2007)
EDNRB (endothelin receptor B) (HUMAN)
EDNRB appears essential for the continued survival of migrating melanocytes Ohyama et al. (2006)
SOX10 interacts with EDNRB which regulates melanocyte SCs. Binding of Tenascin-C to EDNRB may regulate HFeSC niche properties Boissy and Nordlund (1997), Lange et al. (2007), Slominski et al. (2005) and Yoshida et al. (1996)
ESR1 (estrogen receptor ß) (HUMAN)
The estrogen receptor (ESR) is a ligand-activated transcription factor composed of a and ß domain. These receptors display different immunohistochemical localizations in human scalp skin, where ESRß is predominantly expressed, suggesting their different functional roles in cutaneous biology Ohyama et al. (2006)
17-ß-estradiol activates via the ESR jagged1- and notch1 expression. Jagged1 regulates HF differentiation (HFeSC/TA activation), whereas notch signaling is required for the maintenance of melanocyte SCs in the HFAmbler and Watt (2007), Kwon et al. (2004), Nishikawa and Osawa (2007), Soares et al. (2004), Thornton et al. (2003) and Yoo et al. (2007)
FS (follistatin) (HUMAN)
FS is a gonadal protein that inhibits follicle -stimulating hormone release Ohyama et al. (2006)
FS antagonizes the functions of BMPs and activin. Both mediate interactions between the mesenchymal SC and HFeSC within the niche and form an integrated network Hwang et al. (2005), Nakamura et al. (2003) and Thesleff et al. (2007)
GHR (growth hormone receptor) (HUMAN)
Binding of growth hormone (GH) to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. In transgenic rats in which the GH expression is suppressed the hair enters a long-lasting telogen phase Ohyama et al. (2006)
HF bulge cells which express GHR also express prolactin receptors. These two factors play an important role for the immunocompetent bulge region (HFeSC niche)Dardenne et al. (1998) and Umeda-Ikawa et al. (2006)
GR (Nr3c1; glucocorticoid receptor) (Mouse)
Keratinocytes from both the HF bulge and interfollicular epidermis of mice express Nr3c1Ohyama et al. (2006)
GR signaling has an important role in the homeostasis of HFeSC, and they are more sensitive to the antiproliferative effect of glucocorticoids implicating that the reduction in their number may underlie the tumor suppressor effect of Nr3c1 in the skin Chebotaev et al. (2007) and Morris (2007)
Igfbp-3, -5, -6 (insulin-like growth factor binding proteins 3, 5, 6) (Mouse)
Igfbp-3 inhibits hair matrix keratinocyte proliferation, possibly involved in catagen induction. Igfbp-5 involved in hair shaft formation. Igfbp-6 promotes ß-catenin transcriptional activity Blanpain et al. (2004) and Morris et al. (2004)
Igf-1 production stimulated by major hair growth-regulatory hormones, e.g. insulin, prolactin; main effect likely on TA and their more differentiated progeny. Key role of ß-catenin in HFeSC commitment to HF-type differentiation Alonso and Fuchs (2006), Amini Nik et al. (2007), Paus and Foitzik (2004), Paus et al. (2005), (Schlake, 2005a) and (Schlake, 2005b), Stenn and Paus (2001) and Weger and Schlake (2005)
LTBP1 (latent transforming growth factor ß binding protein 1) (HUMAN) (Mouse)
LTBP1 targets latent complexes of TGFß to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. LTBP1 interacts with fibrillin and is a microfibril-associated protein Blanpain et al. (2004) and Ohyama et al. (2006)
TGFß1/2 are catagen-inducing growth factors. TGFß2 is an inducer of HF morphogenesis. Epidermal growth factor stimulated TGFß1 expression in stromal cells, whereas keratinocyte growth factor stimulated TGFß2 in epithelial cells (mobilization and inactivation of HFeSC) (Foitzik et al., 1999) and (Foitzik et al., 2000), Isogai et al. (2003), Itoh et al. (1998), Paus and Foitzik (2004)
Mmp-2 (matrix metallopeptidase) (Mouse)
The Mmp famliy control extracellular matrix remodelling, including during HF cyclingBlanpain et al. (2004)
Expression of Mmp-2 is increased by thymosinß4. Thymosinß4 accelerates hair growth due to its effect on the active phase of the HF cycle. Activation of EGF receptor by the release of Gprc-ligands through proteolytic action of matrix Mmp´s promotes proliferation, survival, differentiation and migration of HFeSC/TA due to remodelling the basement membrane of the HFeSC-niche Karelina et al. (2000), (Paus et al., 1994a) and (Paus et al., 1994b), Philp et al. (2004) and Shah and Catt, 2004
DOWN REGULATED EXPRESSION
ANGPTL7 (angiopoietin-like 7) (HUMAN)
ANGPTL7 is expressed at high levels in the avascular corneal stromal layer suggested that the protein, similar to certain angiopoietins, acts as a negative regulator of angiogenesisOhyama et al. (2006)
Angiopoietins have been identified as the major ligands of the endothelial-specific receptor Tie2. Thus, the Tie2/Angiopoietin-like signaling pathway plays a critical role in maintaining HFeSC in the quiescent state in the niche Kuroda et al. (2001), Mecklenburg et al. (2000), Peek et al. (2002), Suda et al. (2005) and (Yano et al., 2001) and (Yano et al., 2003)
Cyclin G2 (Mouse)
Estradiol represses expression of the cyclin G2 gene, which encodes a negative regulator of the cell cycle Morris et al. (2004)Cyclin G2 may contribute in maintaining the quiescent state of progenitor and/or differentiated cells. Stossi et al. (2006)
Ir1 (interleukin 1 receptor) (Mouse)
The IL-1 system plays a key role in skin physiology and pathology Morris et al. (2004)
Ir1 plays a role in initiation and maintenance of inflammatory reactions of the immune privileged HFeSC niche McGirt and Beck (2006), Palmer et al. (2007) and Schiller et al. (2006)
LTBP2 (latent transforming growth factor ß binding protein) (HUMAN)
It has thus been suggested that LTBP2 may have multiple functions: as a member of the TGF-ß latent complex, as a structural component of microfibrils, and a role in cell adhesion Ohyama et al. (2006)
LTBP2 has a regulatory mechanism of elastic fiber assembly in which LTBP-2 regulates targeting of DANCE on microfibrils to form elastic fibers and this could be a prerequisite for the HFeSC niche Hirai et al. (2007)
Ntf3 (neurotrophin-3) (Mouse)
Ntf3 and its receptor tyrosine kinase C are essential for nervous system development. Both are expressed in human scalp skin and HFs and exert many growth-regulatory functions beyond the nervous system Morris et al. (2004)
Neurotrophins, including NGF, BDNF, NT-3, and NT-4, and their cognate receptors, tyrosine kinase A-C and p75 neurotrophin receptor exhibit significant, hair cycle-dependent fluctuations on the gene and protein level. Related with a loss of quiescence in the HFeSC-niche by modulating the surrounding neural network Adly et al. (2005) and Botchkarev et al. (2004)
PTGER4 (prostaglandin E receptor) (HUMAN)
Knockout studies in mice suggest that PTGER4 may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses Ohyama et al. (2006)
Prostanoid pathway in HF may regulate hair regrowth. Local production of prostaglandin in stem cell compartments controls injury-induced HFeSC proliferation Colombe et al. (2008), Colombe et al. (2007), Kabashima et al. (2003) and Rakoff-Nahoum and Medzhitov (2007)
OTHERS EXPRESSED IN BULGE REGION.
ADM (adrenomedullin) (HUMAN)
ADM is a potent vasodilator, but also exerts other functions, such as regulating cell growth and antimicrobial defence Müller et al. (2003)
Expression of ADM especially in proximity to the bulge region displaying immune privilege (quiescent HFeSC niche conditions) Müller et al. (2003)
Cald1 (caldesmon-1) (Mouse)
Cald1 was present during the early anagen phases within the bulge and is involved in cytoskeleton remodeling processes which could inhibit HF growth Wollina et al. (1995)
Cald1 modulates the actin cytoskeleton in the bulge region and could be therefore a regulator of the HFeSC-niche Greenberg et al. (2008), Hayashi et al. (2002) and Wollina et al. (1995)
CCND1 (cyclin D1) (HUMAN) (Mouse)
CCND1 forms a complex with and functions as a regulatory subunit of the cyclin-dependent kinases-4 or -6, whose activity is required for cell cycle G1/S transition Xu et al. (2003) and Blanpain et al. (2004)
Localized to suprabasal cells of telogen bulge and anagen ORS. Mediate proliferation HFeSCto differentiated TA cells in the suprabasal ORS. NF-kappaB activation is essential for induction of cyclin D1 and SHH expression and hair placode down growth Schmidt-Ullrich et al. (2006) and Xu et al. (2003)
EPO (erythropoietin) (HUMAN)
HFs express EPO and transcripts for EPO-receptor and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1a Bodó et al. (2007) TGFß blocks EPO signaling downstream of c-myc induction through a SMAD3-dependent mechanism Bodó et al. (2007)
HSD17B4 (hydroxysteroid (17-ß) dehydrogenase 4; 17-ß-estradiol) (HUMAN)
It has long been known that estrogens also profoundly alter HF growth and cycling by binding to locally expressed high-affinity estrogen receptors (ESRs) Ohnemus et al. (2006)
Estrogen arrests murine pelage HFs in telogen and demonstrate that it is a potent inducer of premature catagen development. 17-ß-estradiol activates via the ESR JAGGED1- and NOTCH1 expression. JAGGED1 regulates HF differentiation (HFeSC/TA activation) Ambler and Watt (2007), Nishikawa and Osawa (2007), Ohnemus et al. (2005) and Yoo et al. (2007)
NGF-R (nerve growth factor receptor) (HUMAN)
Expression of NGF-R in the bulge region of plucked human HFsMoll (1996)
NGF-R regulates the immune privilege of the HF which is linked to a HFeSC niche(Peters et al., 2006b) and (Peters et al., 2007)
Substance P (HUMAN) (Mouse)
Substance P down-regulates immunoreactivity for the growth-promoting NGF receptor, whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR) Peters et al. (2007)
TMSB4 (thymosin ß4) (HUMAN) (Mouse) Philp et al. (2004)
TMSB4 up-regulates MMP2 and promotes the migration of HFeSCs/TAs to the base of the HF Karelina et al. (2000), Paus et al., 1994a
Vipr1 (vasoactive intestinal peptide (Vip) receptor 1) (Mouse)
It was demonstrated that Vipr1 is expressed sequentially in the bulge area and the IRS as well as in the sebaceous gland epitheliumWollina et al. (1995)
Vipr1 is expressed in the bulge region during anagen V, but is absent during cycle phases. This suggests a physiological function of Vipr1 in terminating the HF growth during anagen I to IV. Additionally Vip could be a regulator for the immunoprivileged bulge (HFeSC-niche)Luger (2002) and Wollina et al. (1995)