胸腺肽β4在眼表疾病中的保护作用
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摘要
胸腺肽是一种在多种组织结构中广泛分布且具有多种生物活性的蛋白。分为三种亚型:胸腺肽α、胸腺肽β、胸腺肽γ。其中胸腺肽β家族中以胸腺肽β4(Tβ4)在正常人体中的分布最为广泛。已有大量研究证实,Tβ4具有抗炎、抗凋亡、促增殖等作用。而眼表疾病大多与眼表上皮的损伤及炎症有关,因此促进损伤修复、愈合及抗炎成为治疗眼表疾病的关键。本文将主要介绍Tβ4的分布、结构、合成及其在眼表疾病中的保护作用。
·Thymosin is a kind of protein that is widely distributed in many tissues. It has many biological activities. Thymosin is divided into three subtypes: thymosin α, thymosin β and thymosin γ. Thymosin β4(Tβ4) is the most widely distributed in normal human body. A large number of studies have confirmed that Tβ4 has the functions of anti-inflammatory, anti-apoptosis and promoting proliferation. Ocular surface diseases are mostly related to ocular surface injury and inflammation. Therefore, promoting wound repair and healing and anti-inflammatory are the key to the treatment of ocular surface diseases. The present review mainly introduces the distribution, structure, synthesis of Tβ4 and its protective effect on ocular surface.
·Thymosin is a kind of protein that is widely distributed in many tissues. It has many biological activities. Thymosin is divided into three subtypes: thymosin α, thymosin β and thymosin γ. Thymosin β4(Tβ4) is the most widely distributed in normal human body. A large number of studies have confirmed that Tβ4 has the functions of anti-inflammatory, anti-apoptosis and promoting proliferation. Ocular surface diseases are mostly related to ocular surface injury and inflammation. Therefore, promoting wound repair and healing and anti-inflammatory are the key to the treatment of ocular surface diseases. The present review mainly introduces the distribution, structure, synthesis of Tβ4 and its protective effect on ocular surface.
引文
1 Goldstein AL, Slater FD, White A.Preparation, assay, and partial purification of a thymic lymphocytopoietic factor (thymosin). Proc Natl Acad Sci U S A 1966;56(3): 1010-1017
2 Dedova IV, Nikolaeva OP, Safer D, et al.Thymosin beta4 induces a conformational change in actin monomers. Biophys J 2006;90(3):985-992
3 Goldstein AL, Hannappel E, Sosne G, et al.Thymosin beta4:a multi-functional regenerative peptide.Basic properties and clinical applications. Expert Opin Biol Ther 2012;12(1):37-51
4 Sosne G, Qiu P, Christopherson PL, et al. Thymosin beta 4 suppression of corneal NFkappaB: a potential anti-inflammatory pathway. Exp Eye Res 2007;84(4):663-669
5 Low TL, Hu SK, Goldstein AL.Complete amino acid sequence of bovine thymosin beta 4:a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A 1981;78(2):1162-1166
6 Hoch K, Volk DE.Structures of Thymosin Proteins. Vitam Horm 2016;102:1-24
7 Jo JO, Kang YJ, Ock MS, et al. Thymosin beta4 expression in human tissues and in tumors using tissue microarrays. Appl Immunohistochem Mol Morphol 2011;19(2):160-167
8 Kuzan A.Thymosin beta as an Actin-binding Protein with a Variety of Functions. Adv Clin Exp Med 2016;25(6):1331-1336
9 Hong Y,Yao Q,Zheng L.Thymosin beta4 attenuates liver fibrosis via suppressing Notch signaling. Biochem Biophys Res Commun 2017;493(4):1396-1401
10 Vasilopoulou E, Winyard PJ, Riley PR, et al.The role of thymosin-beta4 in kidney disease. Expert Opin Biol Ther 2015;15(Suppl 1):S187-190
11 Bollini S, Riley PR, Smart N.Thymosin beta4:multiple functions in protection, repair and regeneration of the mammalian heart. Expert Opin Biol Ther 2015;15(Suppl 1):S163-174
12 Liu CY, Kao WW.Corneal Epithelial Wound Healing. Prog Mol Biol Transl Sci 2015; 134:61-71
13 Sosne G, Chan CC, Thai K, et al.Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo. Exp Eye Res 2001;72(5):605-608
14 Sosne G, Szliter EA, Barrett R, et al. Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res 2002; 74(2):293-299
15 Ardan T, Nemcova L, Bohuslavova B, et al. Reduced Levels of Tissue Inhibitors of Metalloproteinases in UVB-Irradiated Corneal Epithelium. Photochem Photobiol 2016; 92(5):720-727
16 Philp D, Badamchian M, Scheremeta B, et al. Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair Regen 2003;11(1):19-24
17 Sosne G, Xu L, Prach L, et al. Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta. Exp Cell Res 2004;293(1):175-183
18 Kiritsi D, Has C, Bruckner-Tuderman L.Laminin 332 in junctional epidermolysis bullosa. Cell Adh Migr 2013;7(1):135-141
19 Ho JH, Chuang CH, Ho CY, et al. Internalization is essential for the antiapoptotic effects of exogenous thymosin beta-4 on human corneal epithelial cells. Invest Ophthalmol Vis Sci 2007;48(1):27-33
20 Vasilopoulou E, Kolatsi-Joannou M, Lindenmeyer MT, et al. Loss of endogenous thymosin beta4 accelerates glomerular disease. Kidney Int 2016;90(5):1056-1070
21 Zhang J, Wu J, Zeng W, et al.Function of Thymosin Beta-4 in Ethanol-Induced Microglial Activation. Cell Physiol Biochem 2016;38(6):2230-2238
22 Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer 2013;12:86
23 Crnej A, Omoto M, Dohlman TH, et al.Corneal inflammation after miniature keratoprosthesis implantation. Invest Ophthalmol Vis Sci 2014;56(1):185-189
24 Li ZY, Chen ZL, Zhang T, et al. TGF-beta and NF-kappaB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response. Aging (Albany NY) 2016;8(10):2337-2354
25中华医学会眼科学分会角膜病学组.干眼临床诊疗专家共识(2013年).中华眼科杂志2013;49(1):73-75
26 Sosne G, Kim C, Kleinman HK.Thymosin beta4 significantly reduces the signs of dryness in a murine controlled adverse environment model of experimental dry eye. Expert Opin Biol Ther 2015;15(Suppl 1):S155-161
27 Sosne G, Dunn SP, Kim C.Thymosin beta4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea 2015;34(5):491-496
28 Sosne G, Ousler GW.Thymosin beta 4 ophthalmic solution for dry eye:a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model. Clin Ophthalmol 2015;9:877-884
29李轩,姜志昕,郝朋,等.胸腺素β4对体外培养的兔角膜上皮细胞氧化损伤的保护作用.中华眼科杂志 2013;49(8):716-722
30姜志昕,郝朋,汤欣,等.胸腺素β4对乙醇诱导的体外兔角膜上皮细胞损伤的保护作用.中华实验眼科杂志2016;34(2):108-114
2 Dedova IV, Nikolaeva OP, Safer D, et al.Thymosin beta4 induces a conformational change in actin monomers. Biophys J 2006;90(3):985-992
3 Goldstein AL, Hannappel E, Sosne G, et al.Thymosin beta4:a multi-functional regenerative peptide.Basic properties and clinical applications. Expert Opin Biol Ther 2012;12(1):37-51
4 Sosne G, Qiu P, Christopherson PL, et al. Thymosin beta 4 suppression of corneal NFkappaB: a potential anti-inflammatory pathway. Exp Eye Res 2007;84(4):663-669
5 Low TL, Hu SK, Goldstein AL.Complete amino acid sequence of bovine thymosin beta 4:a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A 1981;78(2):1162-1166
6 Hoch K, Volk DE.Structures of Thymosin Proteins. Vitam Horm 2016;102:1-24
7 Jo JO, Kang YJ, Ock MS, et al. Thymosin beta4 expression in human tissues and in tumors using tissue microarrays. Appl Immunohistochem Mol Morphol 2011;19(2):160-167
8 Kuzan A.Thymosin beta as an Actin-binding Protein with a Variety of Functions. Adv Clin Exp Med 2016;25(6):1331-1336
9 Hong Y,Yao Q,Zheng L.Thymosin beta4 attenuates liver fibrosis via suppressing Notch signaling. Biochem Biophys Res Commun 2017;493(4):1396-1401
10 Vasilopoulou E, Winyard PJ, Riley PR, et al.The role of thymosin-beta4 in kidney disease. Expert Opin Biol Ther 2015;15(Suppl 1):S187-190
11 Bollini S, Riley PR, Smart N.Thymosin beta4:multiple functions in protection, repair and regeneration of the mammalian heart. Expert Opin Biol Ther 2015;15(Suppl 1):S163-174
12 Liu CY, Kao WW.Corneal Epithelial Wound Healing. Prog Mol Biol Transl Sci 2015; 134:61-71
13 Sosne G, Chan CC, Thai K, et al.Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo. Exp Eye Res 2001;72(5):605-608
14 Sosne G, Szliter EA, Barrett R, et al. Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res 2002; 74(2):293-299
15 Ardan T, Nemcova L, Bohuslavova B, et al. Reduced Levels of Tissue Inhibitors of Metalloproteinases in UVB-Irradiated Corneal Epithelium. Photochem Photobiol 2016; 92(5):720-727
16 Philp D, Badamchian M, Scheremeta B, et al. Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair Regen 2003;11(1):19-24
17 Sosne G, Xu L, Prach L, et al. Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta. Exp Cell Res 2004;293(1):175-183
18 Kiritsi D, Has C, Bruckner-Tuderman L.Laminin 332 in junctional epidermolysis bullosa. Cell Adh Migr 2013;7(1):135-141
19 Ho JH, Chuang CH, Ho CY, et al. Internalization is essential for the antiapoptotic effects of exogenous thymosin beta-4 on human corneal epithelial cells. Invest Ophthalmol Vis Sci 2007;48(1):27-33
20 Vasilopoulou E, Kolatsi-Joannou M, Lindenmeyer MT, et al. Loss of endogenous thymosin beta4 accelerates glomerular disease. Kidney Int 2016;90(5):1056-1070
21 Zhang J, Wu J, Zeng W, et al.Function of Thymosin Beta-4 in Ethanol-Induced Microglial Activation. Cell Physiol Biochem 2016;38(6):2230-2238
22 Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer 2013;12:86
23 Crnej A, Omoto M, Dohlman TH, et al.Corneal inflammation after miniature keratoprosthesis implantation. Invest Ophthalmol Vis Sci 2014;56(1):185-189
24 Li ZY, Chen ZL, Zhang T, et al. TGF-beta and NF-kappaB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response. Aging (Albany NY) 2016;8(10):2337-2354
25中华医学会眼科学分会角膜病学组.干眼临床诊疗专家共识(2013年).中华眼科杂志2013;49(1):73-75
26 Sosne G, Kim C, Kleinman HK.Thymosin beta4 significantly reduces the signs of dryness in a murine controlled adverse environment model of experimental dry eye. Expert Opin Biol Ther 2015;15(Suppl 1):S155-161
27 Sosne G, Dunn SP, Kim C.Thymosin beta4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea 2015;34(5):491-496
28 Sosne G, Ousler GW.Thymosin beta 4 ophthalmic solution for dry eye:a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model. Clin Ophthalmol 2015;9:877-884
29李轩,姜志昕,郝朋,等.胸腺素β4对体外培养的兔角膜上皮细胞氧化损伤的保护作用.中华眼科杂志 2013;49(8):716-722
30姜志昕,郝朋,汤欣,等.胸腺素β4对乙醇诱导的体外兔角膜上皮细胞损伤的保护作用.中华实验眼科杂志2016;34(2):108-114