成纤维细胞生长因子5研究进展
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摘要
成纤维细胞生长因子5(Fibroblasts growth factor 5,FGF5)是成纤维细胞生长因子家族(FGFs)的成员之一,具备多种生物学功能。目前的研究发现,FGF5在哺乳动物毛发周期性生长中起着重要作用,是生长期到退行期的关键信号分子,同时与动物肢体发育及人多形性胶质母细胞瘤、黑色素瘤、肝细胞癌、人类高血压的形成也有一定的联系。综述了近年来FGF5的相关生物学功能及其在疾病形成中的研究结果,以期为其在人类毛发生长、动物绒毛资源利用、肢体发育以及肿瘤诊治等领域中进一步的研究及合理开发利用提供理论依据。
FGF5(fibroblast growth factor 5,FGF5)is a member of fibroblast growth factors(FGFs),which possesses a variety of biological functions. Previous studies have found that FGF5 plays an important role in the cyclical growth of mammalian hair and is a key signal molecule from anagen to catagen. FGF5 also involves in animal limb development,human glioblastoma multiforme,melanoma,hepatocellular carcinoma and hypertension. In this paper,we review the biological functions of FGF5 and the related research results in disease formation in recent years,aiming at providing theoretical basis for its further research and rational utilization in the fields of human hair growth,animal villus resources utilization,limb development,and tumor diagnosis and treatment.
FGF5(fibroblast growth factor 5,FGF5)is a member of fibroblast growth factors(FGFs),which possesses a variety of biological functions. Previous studies have found that FGF5 plays an important role in the cyclical growth of mammalian hair and is a key signal molecule from anagen to catagen. FGF5 also involves in animal limb development,human glioblastoma multiforme,melanoma,hepatocellular carcinoma and hypertension. In this paper,we review the biological functions of FGF5 and the related research results in disease formation in recent years,aiming at providing theoretical basis for its further research and rational utilization in the fields of human hair growth,animal villus resources utilization,limb development,and tumor diagnosis and treatment.
引文
[1]Zhan X, Bates B, Hu XG, et al. The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors[J]. Molecular&Cellular Biology, 1988, 8(8):3487-3495.
[2]Hébert JM, Rosenquist T, G?tz J, et al. FGF5 as a regulator of the hair growth cycle:Evidence from targeted and spontaneous mutations[J]. Cell, 1994, 78(6):1017-1025.
[3]Clase KL, Mitchell PJ, Ward PJ, et al. FGF5 stimulates expansion of connective tissue fibroblasts and inhibits skeletal muscle development in the limb[J]. Developmental Dynamics, 2000, 219(3):368-380.
[4]Allerstorfer S, Pirker C, Spiegl-Kreinecker S, et al. Autocrine and paracrine contributions of FGF5 to the malignant progression of human astrocytic brain tumors[J]. Neuro-Oncology, 2008, 10(6):1147-1147.
[5]Allerstorfer S, Sonvilla GH, Spiegl-Kreinecker S, et al. FGF5 as an oncogenic factor in human glioblastoma multiforme:autocrine and paracrine activities[J]. Oncogene, 2008, 27(30):4180-4190.
[6]BergerW,AllerstorferS,FischerH,etal.FGF5/FGFR1-mediated signals as therapeutic targets in human glioblastoma multiforme[J]. Cancer Research, 2009, 69(9):18-22.
[7]Ghassemi S, Vejdovszky K, Sahin E, et al. FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo[J].Oncotarget, 2017, 8(50):87750.
[8]Feng F, Rui-Min C, Lei Y, et al. MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma[J]. Journal of Hepatology, 2015, 63(4):874-885.
[9]Liu C, Li H, Qi Q, et al. Common variants in or near FGF5,CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans[J]. Journal of Hypertension, 2011,29(1):70-75.
[10]Suzuki S, Kato T, Takimoto H, et al. Localization of rat FGF-5protein in skin macrophage-like cells and FGF-5S protein in hair follicle:possible involvement of two Fgf-5 gene products in hair growth cycle regulation[J]. Journal of Investigative Dermatology,1998, 111(6):963-972.
[11]He XL, Yuan C, Chen YL. Isolation, characterization, and expression analysis of FGF5, isoforms in cashmere goat[J].Small Ruminant Research, 2014, 116(2-3):111-117.
[12]Suzuki S, Ota Y, Ozawa K, et al. Dual-mode regulation of hair growth cycle by two Fgf-5, gene products[J]. Journal of Investigative Dermatology, 2000, 114(3):456-463.
[13]Ota Y, Saitoh Y, Suzuki S, et al. Fibroblast growth factor 5 inhibits hair growth by blocking dermal papilla cell activation[J].Biochemical&Biophysical Research Communications, 2002, 290(1):169-176.
[14]Rosenquist TA, Martin GR. Fibroblast growth factor signalling in the hair growth cycle:expression of the fibroblast growth factor receptor and ligand genes in the murine hair follicle[J].Developmental Dynamics, 2010, 205(4):379-386.
[15]BeenkenA,MohammadiM.TheFGFfamily:biology,pathophysiologyandtherapy[J].NatureReviewsDrug Discovery, 2009, 8(3):235-253.
[16]Ornitz DM, Itoh N. The Fibroblast Growth Factor signaling pathway.[J]. Wiley Interdiscip Rev Dev Biol, 2015, 4(3):215-266.
[17]Su YH, Du H, Niu GM, et al. The fibroblast growth factor signaling pathway[J]. Chinese Journal of Tissue Engineering Research,2016, 20(15):2255-2264.
[18]Chase HB. Growth of the hair[J]. Physiological Reviews, 1954,34(1):113.
[19]Dr?gemüller C, Rüfenacht S, Wichert B, et al. Mutations within the FGF5, gene are associated with hair length in cats[J]. Animal Genetics, 2007, 38(3):218-221.
[20]Dierks C, M?mke S, Philipp U, et al. Allelic heterogeneity of FGF5mutations causes the long-hair phenotype in dogs[J]. Animal Genetics, 2013, 44(4):425-431.
[21]Mizuno S, Iijima S, Okano T, et al. Retrotransposon-mediated Fgf5(go-Utr)mutant mice with long pelage hair[J]. Experimental Animals, 2011, 60(2):161-167.
[22]Yoshizawa Y, Wada K, Shimoi G, et al. A 1-bp deletion in Fgf5,causes male-dominant long hair in the Syrian hamster[J].Mammalian Genome, 2016, 27(1-2):98.
[23]Yu F, Liu Z, Jiao S, et al. A nonsense mutation in the FGF5 gene is associated with the long-haired phenotype in domestic guinea pigs(Cavia porcellus)[J]. Animal Genetics, 2018, 49(3):269.
[24]Mulsant P, Rochambeau HD, Thébault RG. A note on the linkage between the angora and Fgf5 genes in rabbits[J]. World Rabbit Science, 2010, 12(1):13.
[25]Li CX, Jiang MS, Chen SY, et al. Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits[J]. Hereditas, 2008, 30(7):893.
[26]Legrand R, Tiret L, Abitbol M. Two recessive mutations in FGF5are associated with the long-hair phenotype in donkeys[J].Genetics Selection Evolution, 46, 1(2014-09-25), 2014, 46(1):1-7.
[27]Wang X, Bei C, Zhou J, et al. Disruption of FGF5 in cashmere goats using CRISPR/Cas9 results in more secondary hair follicles and longer fibers[J]. PLoS One, 2016, 11(10):e0164640.
[28]Li W, Liu C, Zhang X, et al. CRISPR/Cas9-mediated loss of FGF5function increases wool staple length in sheep[J]. Febs Journal,2017, 284(17):2764-2773.
[29]Zhang B, Chang L, Lan YX, et al. Genome-wide definition of selective sweeps reveals molecular evidence of trait-driven domestication among elite goat(Capra species)breeds for the production of dairy, cashmere, and meat[J]. Giga Science, 2018, 7(12):doi:10.1093/gigasciencelgiy105.
[30]Ma T, Li J, Jiang Q, et al. Differential expression of miR-let7a in hair follicle cycle of Liaoning cashmere goats and identification of its targets[J]. Functional&Integrative Genomics, 2018, 18(6):701-707.
[31]Zhao B, Chen Y, Hao Y, et al. Transcriptomic analysis reveals differentially expressed genes associated with wool length in rabbit[J]. Animal Genetics, 2018, 49(5):428-437.
[32]Chen Z, Wang Z, Xu S, et al. Characterization of hairless(Hr)and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans[J]. Bmc Evolutionary Biology, 2013, 13(1):34.
[33]Seago SV, Ebling FJ. The hair cycle on the human thigh and upper arm[J]. British Journal of Dermatology, 1985, 113(1):9-16.
[34]Wang K, Li M, Hakonarson H. ANNOVAR:functional annotation of genetic variants from high-throughput sequencing data[J].Nucleic Acids Research, 2010, 38(16):e164.
[35]Higgins CA, Petukhova L, Harel S, et al. FGF5 is a crucial regulator of hair length in humans[J]. Proc Natl Acad Sci USA, 2014, 111(29):10648-10653.
[36]Burg D, Yamamoto M, Namekata M, et al. Promotion of anagen,increased hair density and reduction of hair fall in a clinical setting following identification of FGF5-inhibiting compounds via a novel 2-stage process[J]. Clinical Cosmetic&Investigational Dermatology, 2017, 10:71-85.
[37]Gilbert SF. Developmental Biology[M]. 7th Edition. Sunderland Massachusetts:Sinauer Associates Inc, 2003.
[38]Martin GR. The roles of FGFs in the early development of vertebrate limbs[J]. Genes&Development, 1998, 12(11):1571.
[39]Puputti M, Tynninen O, Sihto H, et al. Amplification of KIT,PDGFRA, VEGFR2, and EGFR in gliomas[J]. Molecular Cancer Research Mcr, 2006, 4(12):927.
[40]Allerstorfer S, Sonvilla GH, Spiegl-Kreinecker S, et al. FGF5 as an oncogenic factor in human glioblastoma multiforme:autocrine and paracrine activities.[J]. Oncogene, 2008, 27(30):4180-4190.
[41]Morrison RS, Yamaguchi F, Bruner JM, et al. Fibroblast growth factor receptor gene expression and immunoreactivity are elevated in human glioblastoma multiforme[J]. Cancer Research, 1994,54(10):2794.
[42]Stachowiak MK, Maher PA, Joy A, et al. Nuclear localization of functional FGF receptor 1 in human astrocytes suggests a novel mechanism for growth factor action[J]. Brain Research Molecular Brain Research, 1996, 38(1):161.
[43]Wang Y, Becker D. Antisense targeting of basic fibroblast growth factor and dibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth[J]. Nature Medicine, 1997, 3(8):887-893.
[44]Nesbit M, Nesbit HJ, Andl T, et al. Basic fibroblast growth factor inducesatransformed phenotype innormalhuman melanocytes[J]. Oncogene, 1999, 18(47):6469-6476.
[45]Buendia MA, Neuveut C. Hepatocellular carcinoma[J]. Cold Spring Harbor Perspectives in Medicine, 2015, 5(2):469-470.
[46]Gao Y, Chen G, Tian H, et al. Prevalence of hypertension in China:A cross-sectional study[J]. PLoS One, 2013, 8(6):e65938.
[47]AlcocerL,CuetoL.Hypertension,ahealtheconomics perspective[J]. Therapeutic Advances in Cardiovascular Disease, 2008, 2(3):147-155.
[48]Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the joint national committee on prevention, detection, evaluation,and treatment of high blood pressure[J]. Acc Current Journal Review, 2015, 12(4):31-32.
[49]Levy D, Ehret GB, Rice K, et al. Genome-wide association study of blood pressure and hypertension[J]. Nature Genetics, 2009, 41(6):677-687.
[50]Li J, Shi J, Huang W, et al. Variant near FGF5 has stronger effects on blood pressure in Chinese with a higher body mass index[J].American Journal of Hypertension, 2015, 28(8):1031-1037.
[51]Fu L, Zhang M, Hu YQ, et al. Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population[J]. Gene,2018, 679:320-327.
[52]Ren Y, Jiao X, Zhang L. Expression level of fibroblast growth factor5(FGF5)in the peripheral blood of primary hypertension and its clinical significance[J]. Saudi Journal of Biological Sciences,2018, 25(3):469-473.
[2]Hébert JM, Rosenquist T, G?tz J, et al. FGF5 as a regulator of the hair growth cycle:Evidence from targeted and spontaneous mutations[J]. Cell, 1994, 78(6):1017-1025.
[3]Clase KL, Mitchell PJ, Ward PJ, et al. FGF5 stimulates expansion of connective tissue fibroblasts and inhibits skeletal muscle development in the limb[J]. Developmental Dynamics, 2000, 219(3):368-380.
[4]Allerstorfer S, Pirker C, Spiegl-Kreinecker S, et al. Autocrine and paracrine contributions of FGF5 to the malignant progression of human astrocytic brain tumors[J]. Neuro-Oncology, 2008, 10(6):1147-1147.
[5]Allerstorfer S, Sonvilla GH, Spiegl-Kreinecker S, et al. FGF5 as an oncogenic factor in human glioblastoma multiforme:autocrine and paracrine activities[J]. Oncogene, 2008, 27(30):4180-4190.
[6]BergerW,AllerstorferS,FischerH,etal.FGF5/FGFR1-mediated signals as therapeutic targets in human glioblastoma multiforme[J]. Cancer Research, 2009, 69(9):18-22.
[7]Ghassemi S, Vejdovszky K, Sahin E, et al. FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo[J].Oncotarget, 2017, 8(50):87750.
[8]Feng F, Rui-Min C, Lei Y, et al. MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma[J]. Journal of Hepatology, 2015, 63(4):874-885.
[9]Liu C, Li H, Qi Q, et al. Common variants in or near FGF5,CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans[J]. Journal of Hypertension, 2011,29(1):70-75.
[10]Suzuki S, Kato T, Takimoto H, et al. Localization of rat FGF-5protein in skin macrophage-like cells and FGF-5S protein in hair follicle:possible involvement of two Fgf-5 gene products in hair growth cycle regulation[J]. Journal of Investigative Dermatology,1998, 111(6):963-972.
[11]He XL, Yuan C, Chen YL. Isolation, characterization, and expression analysis of FGF5, isoforms in cashmere goat[J].Small Ruminant Research, 2014, 116(2-3):111-117.
[12]Suzuki S, Ota Y, Ozawa K, et al. Dual-mode regulation of hair growth cycle by two Fgf-5, gene products[J]. Journal of Investigative Dermatology, 2000, 114(3):456-463.
[13]Ota Y, Saitoh Y, Suzuki S, et al. Fibroblast growth factor 5 inhibits hair growth by blocking dermal papilla cell activation[J].Biochemical&Biophysical Research Communications, 2002, 290(1):169-176.
[14]Rosenquist TA, Martin GR. Fibroblast growth factor signalling in the hair growth cycle:expression of the fibroblast growth factor receptor and ligand genes in the murine hair follicle[J].Developmental Dynamics, 2010, 205(4):379-386.
[15]BeenkenA,MohammadiM.TheFGFfamily:biology,pathophysiologyandtherapy[J].NatureReviewsDrug Discovery, 2009, 8(3):235-253.
[16]Ornitz DM, Itoh N. The Fibroblast Growth Factor signaling pathway.[J]. Wiley Interdiscip Rev Dev Biol, 2015, 4(3):215-266.
[17]Su YH, Du H, Niu GM, et al. The fibroblast growth factor signaling pathway[J]. Chinese Journal of Tissue Engineering Research,2016, 20(15):2255-2264.
[18]Chase HB. Growth of the hair[J]. Physiological Reviews, 1954,34(1):113.
[19]Dr?gemüller C, Rüfenacht S, Wichert B, et al. Mutations within the FGF5, gene are associated with hair length in cats[J]. Animal Genetics, 2007, 38(3):218-221.
[20]Dierks C, M?mke S, Philipp U, et al. Allelic heterogeneity of FGF5mutations causes the long-hair phenotype in dogs[J]. Animal Genetics, 2013, 44(4):425-431.
[21]Mizuno S, Iijima S, Okano T, et al. Retrotransposon-mediated Fgf5(go-Utr)mutant mice with long pelage hair[J]. Experimental Animals, 2011, 60(2):161-167.
[22]Yoshizawa Y, Wada K, Shimoi G, et al. A 1-bp deletion in Fgf5,causes male-dominant long hair in the Syrian hamster[J].Mammalian Genome, 2016, 27(1-2):98.
[23]Yu F, Liu Z, Jiao S, et al. A nonsense mutation in the FGF5 gene is associated with the long-haired phenotype in domestic guinea pigs(Cavia porcellus)[J]. Animal Genetics, 2018, 49(3):269.
[24]Mulsant P, Rochambeau HD, Thébault RG. A note on the linkage between the angora and Fgf5 genes in rabbits[J]. World Rabbit Science, 2010, 12(1):13.
[25]Li CX, Jiang MS, Chen SY, et al. Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits[J]. Hereditas, 2008, 30(7):893.
[26]Legrand R, Tiret L, Abitbol M. Two recessive mutations in FGF5are associated with the long-hair phenotype in donkeys[J].Genetics Selection Evolution, 46, 1(2014-09-25), 2014, 46(1):1-7.
[27]Wang X, Bei C, Zhou J, et al. Disruption of FGF5 in cashmere goats using CRISPR/Cas9 results in more secondary hair follicles and longer fibers[J]. PLoS One, 2016, 11(10):e0164640.
[28]Li W, Liu C, Zhang X, et al. CRISPR/Cas9-mediated loss of FGF5function increases wool staple length in sheep[J]. Febs Journal,2017, 284(17):2764-2773.
[29]Zhang B, Chang L, Lan YX, et al. Genome-wide definition of selective sweeps reveals molecular evidence of trait-driven domestication among elite goat(Capra species)breeds for the production of dairy, cashmere, and meat[J]. Giga Science, 2018, 7(12):doi:10.1093/gigasciencelgiy105.
[30]Ma T, Li J, Jiang Q, et al. Differential expression of miR-let7a in hair follicle cycle of Liaoning cashmere goats and identification of its targets[J]. Functional&Integrative Genomics, 2018, 18(6):701-707.
[31]Zhao B, Chen Y, Hao Y, et al. Transcriptomic analysis reveals differentially expressed genes associated with wool length in rabbit[J]. Animal Genetics, 2018, 49(5):428-437.
[32]Chen Z, Wang Z, Xu S, et al. Characterization of hairless(Hr)and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans[J]. Bmc Evolutionary Biology, 2013, 13(1):34.
[33]Seago SV, Ebling FJ. The hair cycle on the human thigh and upper arm[J]. British Journal of Dermatology, 1985, 113(1):9-16.
[34]Wang K, Li M, Hakonarson H. ANNOVAR:functional annotation of genetic variants from high-throughput sequencing data[J].Nucleic Acids Research, 2010, 38(16):e164.
[35]Higgins CA, Petukhova L, Harel S, et al. FGF5 is a crucial regulator of hair length in humans[J]. Proc Natl Acad Sci USA, 2014, 111(29):10648-10653.
[36]Burg D, Yamamoto M, Namekata M, et al. Promotion of anagen,increased hair density and reduction of hair fall in a clinical setting following identification of FGF5-inhibiting compounds via a novel 2-stage process[J]. Clinical Cosmetic&Investigational Dermatology, 2017, 10:71-85.
[37]Gilbert SF. Developmental Biology[M]. 7th Edition. Sunderland Massachusetts:Sinauer Associates Inc, 2003.
[38]Martin GR. The roles of FGFs in the early development of vertebrate limbs[J]. Genes&Development, 1998, 12(11):1571.
[39]Puputti M, Tynninen O, Sihto H, et al. Amplification of KIT,PDGFRA, VEGFR2, and EGFR in gliomas[J]. Molecular Cancer Research Mcr, 2006, 4(12):927.
[40]Allerstorfer S, Sonvilla GH, Spiegl-Kreinecker S, et al. FGF5 as an oncogenic factor in human glioblastoma multiforme:autocrine and paracrine activities.[J]. Oncogene, 2008, 27(30):4180-4190.
[41]Morrison RS, Yamaguchi F, Bruner JM, et al. Fibroblast growth factor receptor gene expression and immunoreactivity are elevated in human glioblastoma multiforme[J]. Cancer Research, 1994,54(10):2794.
[42]Stachowiak MK, Maher PA, Joy A, et al. Nuclear localization of functional FGF receptor 1 in human astrocytes suggests a novel mechanism for growth factor action[J]. Brain Research Molecular Brain Research, 1996, 38(1):161.
[43]Wang Y, Becker D. Antisense targeting of basic fibroblast growth factor and dibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth[J]. Nature Medicine, 1997, 3(8):887-893.
[44]Nesbit M, Nesbit HJ, Andl T, et al. Basic fibroblast growth factor inducesatransformed phenotype innormalhuman melanocytes[J]. Oncogene, 1999, 18(47):6469-6476.
[45]Buendia MA, Neuveut C. Hepatocellular carcinoma[J]. Cold Spring Harbor Perspectives in Medicine, 2015, 5(2):469-470.
[46]Gao Y, Chen G, Tian H, et al. Prevalence of hypertension in China:A cross-sectional study[J]. PLoS One, 2013, 8(6):e65938.
[47]AlcocerL,CuetoL.Hypertension,ahealtheconomics perspective[J]. Therapeutic Advances in Cardiovascular Disease, 2008, 2(3):147-155.
[48]Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the joint national committee on prevention, detection, evaluation,and treatment of high blood pressure[J]. Acc Current Journal Review, 2015, 12(4):31-32.
[49]Levy D, Ehret GB, Rice K, et al. Genome-wide association study of blood pressure and hypertension[J]. Nature Genetics, 2009, 41(6):677-687.
[50]Li J, Shi J, Huang W, et al. Variant near FGF5 has stronger effects on blood pressure in Chinese with a higher body mass index[J].American Journal of Hypertension, 2015, 28(8):1031-1037.
[51]Fu L, Zhang M, Hu YQ, et al. Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population[J]. Gene,2018, 679:320-327.
[52]Ren Y, Jiao X, Zhang L. Expression level of fibroblast growth factor5(FGF5)in the peripheral blood of primary hypertension and its clinical significance[J]. Saudi Journal of Biological Sciences,2018, 25(3):469-473.