[1]朱子诚,展欣,张楚,等.转录活性蛋白1在实验性近视眼豚鼠巩膜重塑中对I型胶原表达的调控作用[J].眼科新进展,2019,39(5):415-418.[doi:10.13389/j.cnki.rao.2019.0095]
　ZHU Zi-Cheng,ZHAN Xin,ZHANG Chu,et al.Effect of specificity protein 1 （Sp1）transcription factor on the expression of type I collagen in sclera remodeling of experimentally myopic guinea pigs[J].Recent Advances in Ophthalmology,2019,39(5):415-418.[doi:10.13389/j.cnki.rao.2019.0095]
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转录活性蛋白1在实验性近视眼豚鼠巩膜重塑中对I型胶原表达的调控作用/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
39卷
期数:
2019年5期
页码:
415-418
栏目:
实验研究
出版日期:
2019-05-05

文章信息/Info

Title:
Effect of specificity protein 1 （Sp1）transcription factor on the expression of type I collagen in sclera remodeling of experimentally myopic guinea pigs
作者:
朱子诚; 展欣; 张楚; 刘夏薇; 应充慧; 孙思勤; 柯根杰
230001　安徽省合肥市，中国科学技术大学附属第一医院眼科（安徽省立医院）
Author(s):
ZHU Zi-Cheng; ZHAN Xin; ZHANG Chu; LIU Xia-Wei; YING Chong-Hui; SUN Si-Qin; KE Gen-Jie
Department of Ophthalmology，the First Affiliated Hospital of Science and Technology University of China（Anhui Provincial Hospital），Hefei 230001，Anhui Province，China
关键词:
巩膜重塑; 实验性近视; 转化生长因子-β1; Ⅰ型胶原; 转录活性蛋白1
Keywords:
sclera remodeling; experimental myopia; transforming growth factor-β1; Collagen Ⅰ; specificity protein 1
分类号:
R778.1
DOI:
10.13389/j.cnki.rao.2019.0095
文献标志码:
A
摘要:
目的　研究近视巩膜重塑中转录活性蛋白1（specificity protein 1，Sp1）作为转化生长因子-β1（transforming growth factor-β1，TGF-β1）下游信号转录因子的表达情况和调节I型胶原（Collagen Ⅰ）表达的作用。方法　出生7 d的有色豚鼠75只，随机选取50只左眼使用6号无色半透明乳胶气球作为头套诱导形觉剥夺性近视（form deprivation myopia，FDM）动物模型为FDM组，右眼作为自身对照组，另外25只不作处理为正常组。记录各组豚鼠屈光度及眼轴长度变化。Western blot和RT-PCR检测正常组和FDM组豚鼠遮盖后0周（遮盖前）、2周、4周、6周及遮盖4周去遮盖1周（4/-1周）时巩膜中Sp1和Collagen Ⅰ蛋白和mRNA的表达变化，并分析两者的关系。结果　FDM组豚鼠眼随着遮盖时间延长，由遮盖前远视状态逐渐变为近视状态，眼轴长度也逐渐增长。与正常组相比，FDM组巩膜内Sp1和Collagen Ⅰ的蛋白和mRNA表达均下调，且随遮盖时间的延长，其表达不断减弱。正常组及FDM组遮盖后0周、2周、4周、4/-1周、6周，Sp1蛋白相对表达量分别为1.864±0.014、1.856±0.016、1.215±0.016、0.752±0.013、0.945±0.017、0.518±0.012；Collagen Ⅰ蛋白相对表达量分别为2.922±0.005、2.836±0.001、2.336±0.002、1.500±0.003、1.754±0.006、1.082±0.001；Sp1 mRNA：0.599±0.025、0.557±0.024、0.510±0.013、0.349±0.013、0.457±0.009、0.168±0.012；Collagen Ⅰ mRNA：1.071±0.014、1.010±0.021、0.947±0.006、0.626±0.010、0.770±0.020、0.331±0.004。遮盖2周后各时间点与正常组相比，Sp1和Collagen Ⅰ蛋白和mRNA表达差异均有统计学意义（均为P<0.05）。Sp1与Collagen Ⅰ的蛋白和mRNA表达均呈明显正相关（均为r=1.00，P<0.05）。结论　Sp1作为TGF-β1的下游信号转录因子可能参与了近视巩膜重塑中Collagen Ⅰ的调控，提示Sp1信号转录因子可能通过TGF-β1-Sp1-Collagen Ⅰ信号通路在近视巩膜重塑中发挥重要作用。
Abstract:
Objective　To investigate the expression of transcriptional specificity protein 1 （Sp1） as a downstream transcription factor of transforming growth factor-β1 （TGF-β1） and its regulation on the expression of Collagen Ⅰ in myopic sclera collagen remodeling in guinea pigs.Methods　Totally 75 seven-day’s guinea pigs were studied：the left eyes of 50 guinea pigs，which were randomly selected to induce form deprivation myopia （FDM） with No.6 colorless translucent latex balloons （FDM group），and the uncovered right eyes as self-control group；the other 25 as normal group were untreated.Changes in refractive power and axial length were measured and recorded at each group.Collagen Ⅰ and Sp1 mRNA and protein expression in normal group and FDM group，in which the left eyes were covered for 0 week，2 weeks，4 weeks，6 weeks and FDM recovery 1 week after 4 weeks treatment （4/-1 weeks），were detected via Western bolt and RT-PCR，and their relationship was analyzed.Results　With the coverage time prolonging，refractive state in the FDM group gradually became myopic state，while the axial length was gradually prolonged.Compared with the data of the normal group，Sp1 and Collagen Ⅰ protein and mRNA expression in the FDM sclera were gradually weakened with the prolonged coverage time.The relative expression levels of Sp1 protein in the normal group and the FDM group at 0 week，2 weeks，4 weeks，4/-1 weeks and 6 weeks were 1.864±0.014，1.856±0.016，1.215±0.016，0.752±0.013，0.945±0.017，0.518±0.012，respectively；Collagen Ⅰ protein：2.922±0.005，2.836±0.001，2.336±0.002，1.500±0.003，1.754±0.006，1.082±0.001，respectively；Sp1 mRNA：0.599±0.025，0.557±0.024，0.510±0.013，0.349±0.013，0.457±0.009，0.168±0.012，respectively；Collagen Ⅰ mRNA：1.071±0.014，1.010±0.021，0.947±0.006，0.626±0.010，0.770±0.020，0.331±0.004，respectively.After 2 weeks covering，compared to the normal group at different time points，Sp1 and Collagen Ⅰ protein and mRNA expression were found significant difference statistically （all P<0.05） and an obvious correlation respectively （all r=1.00，all P<0.05）.Conclusion　As the downstream transcription factor of TGF-β1，Sp1 is likely to take part in regulating the synthesis of Collagen Ⅰ in myopic sclera remodeling，suggesting that Sp1 plays an important role in myopic sclera remodeling through TGF-β1-Sp1-Collagen Ⅰ signal transduction pathway.

参考文献/References:

［1］　CHUANG A Y.How to effectively manage myopia［J］？Taiwan J Ophthalmol，2017，7（1）：44-47.
［2］　WANG L，DU M，YI H，DUAN S，GUO W，QIN P，et al.Prevalence of and factors associated with myopia in inner mongolia medical students in China，a cross-sectional study［J］.BMC Ophthalmol，2017，17（1）：52.
［3］　LI M，YUAN Y，CHEN Q，ME R，GU Q，YU Y，et al.Expression of wnt/β-catenin signaling pathway and its regulatory role in type Ⅰ collagen with TGF-β1 in scleral fibroblasts from an experimentally induced myopia guinea pig model［J］.J Ophthalmol，2016，2016：5126560.
［4］　FU X Y，ZHANG X F，XIA W，ZHONG L，WANG Y M，SUN Z T，et al.Effects of 530 nm monochromatic light on basic fibroblast growth factor and transforming growth factor-β1 expression in Müller cells［J］.Int J Ophthalmol，2015，8（5）：904-909.
［5］　YUAN Y，LI M，CHEN Q，ME R，YU Y，GU Q，et al.Crosslinking enzyme lysyl oxidase modulates scleral remodeling in form-deprivation myopia［J］.Curr Eye Res，2017，14（1）：1-8.
［6］　JIANG L，ZHOU Y，XIONG M，FANG L，WEN P，CAO H，et al.Sp1 mediates microRNA-29c-regulated type Ⅰ collagen production in renal tubular epithelial cells［J］.Exp Cell Res，2013，319（14）：2254-2265.
［7］　KIM C R，KIM Y M，LEE M K，KIM I H，CHOI Y H，NAM T J.Pyropia yezoensis peptide promotes collagen synthesis by activating the TGF-β/Smad signaling pathway in the human dermal fibroblast cell line Hs27［J］.Int J Mol Med，2017，39（1）：31-38.
［8］　YAVROPOULOU M P，KOLLIA P，ChATZIDIMITRIOU D，SAMARA S，SKOURA L，YOVOS J G.Severe osteoporosis with multiple spontaneous vertebral fractures in a young male carrying triple polymorphisms in the vitamin D receptor，collagen type 1，and low-density lipoprotein receptor-related peptide 5 genes［J］.Hormones （Athens），2016，15（4）：551-556.
［9］　LIU Y，WANG Y，LV H，JIANG X，ZHANG M，LI X.α-adrenergic agonist brimonidine control of experimentally induced myopia in guinea pigs：A pilot study［J］.Mol Vis，2017，23：785-798.
［10］　HU H，ZHAO G，WU R，ZHONG H，FANG M，DENG H.Axial length/corneal radius of curvature ratio assessment of posterior sclera reinforcement for pathologic myopia［J］.Ophthalmologica，2018，239（2-3）：128-132.
［11］　CAMPBELL I C，SHERWOOD J M，OVERBY D R，HANNON B G，READ A T，RAYKIN J，et al.Quantification of scleral biomechanics and collagen fiber alignment［J］.Methods Mol Biol，2018，1695：135-159.
［12］　GIRARD M J，DAHLMANN-NOOR A，RAYAPUREDDI S，BECHARA J A，BERTIN B M，JONES H，et al.Quantitative mapping of scleral fiber orientation in normal rat eyes［J］.Invest Ophthalmol Vis Sci，2011，52（13）：9684-9693.
［13］　MENG B，LI S M，YANG Y，YANG Z R，SUN F，KANG M T，et al.The association of TGF-β1 genetic polymorphisms with high myopia：a systematic review and meta-analysis［J］.Int J Clin Exp Med，2015，8（11）：20355-20367.
［14］　ZHANG L L，LIU Q，YU J，TANG X J，XU J.Effects of TGF-β on cellular proliferation and α-SMA expression in guinea pig scleral fibroblasts［J］.Rec Adv Ophthalmol，2016，36（11）：1011-1015.
张兰兰，刘琼，于健，唐小娟，徐静.转化生长因子-β（TGF-β）影响豚鼠巩膜成纤维细胞增殖和α-平滑肌肌动蛋白（α-SMA）表达的研究［J］，眼科新进展，2016，36（11）：1011-1015.
［15］　MENG Q，WANG S，TANG W，WU S，GAO N，ZHANG C，et al.XRCC1 mediated the development of cervival cancer through a novel Sp1/Krox-20 swich［J］.Oncotarget，2017，49 （8）：86217-86226.
［16］　HIBINO E，INOUE R，SUGIYAMA M，KUWAHARA J，MATSUZAKI K，HOSHINO M.Identification of heteromolecular binding sites in transcription factors Sp1 and TAF4 using high-resolution nuclear magnetic resonance spectroscopy［J］.Protein Sci，2017，26（11）：2280-2290.
［17］　YU J，LUO H，LI N，DUAN X.Suppression of type Ⅰ collagen expression by miR-29b via PI3K，Akt，and Sp1 pathway，Part Ⅱ：An in vivo investigation［J］.Invest Ophthalmol Vis Sci，2015，56（10）：6019-6028.
［18］　LI J，DU S，SHENG X，LIU J，CEN B，HUANG F，et al.MicroRNA-29b inhibits endometrial fibrosis by regulating the Sp1-TGF-β1/Smad-CTGF axis in a rat model［J］.Reprod Sci，2016，23（3）：386-394.

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备注/Memo

备注/Memo:
安徽省自然科学基金面上项目（编号：1508085MH188）；安徽省教育厅教研项目（编号：2016jyxm0546）
更新日期/Last Update: 2019-05-14