Scientia Agricultura Sinica ›› 2016, Vol. 49 ›› Issue (11): 2203-2213.doi: 10.3864/j.issn.0578-1752.2016.11.016

• ANIMAL SCIENCE·VETERINARY SCIENCERE·SOURCE INSECT • Previous Articles     Next Articles

Study on the Temporal and Spatial Expression and Correlation Analysis of Smads and YAP1 Gene in the Hippo Pathway in Sheep Muscle Tissue

Bao Jian-jun1, Su Rui1, Wang Qing-zeng1, LÜ Xiao-yang1, Gao Wen1, Yu Jia-rui1, Wang Li-hong1,  Chen Ling2, Wu Wen-zhong2, Sheng Shui-xing2, Zhou Hong3, Sun Wei1, Dai Guo-jun1   

  1. 1Animal Science and Technology College, Yangzhou University, Yangzhou 225009, Jiangsu
    2Animal Science and Veterinary Medicine Bureau of Suzhou, Suzhou 215200, Jiangsu
    3Forestation, Herding, Fishing Bureau of Suining Country of Xuzhou, Suining 221200, Jiangsu
  • Received:2015-12-03 Online:2016-06-01 Published:2016-06-01

Abstract: 【Objective】 In order to explore the expression pattern and inner connection between the different genes, the mRNA expression level was used to detect the spatial and temporal expression of genes in TGF-β/Smad signaling pathway of sheep muscle tissue. 【Method】 In this study, q-PCR was used to detect relative expression of Smads genes and Yes-associated protein 1(YAP1) in 2 different skeletal muscles (i.e., gastrocnemius muscle, extensor digitorum longus) and 3 different growth stages (i.e., 2-day-old, 2 and 6-month-old) of Hu Sheep, and analyze the relative expression between Smads(Smad2, Smad3, Smad4 and Smad7) and YAP1. 【Result】The results of the spatial and temporal expression of Smads in TGF-β/Smad signaling pathway showed that the expression of Smads in extensor digitorum longus were lower than in gastrocnemius muscle, which may be related to two different parts of the skeletal muscle. The expression of Smad2, Smad3 and Smad4 genes in the 2-day-old were higher than other growth stages, and Smad7 gene expression in the 2-day-old was lower than 6-month-old, and the expression in 2-month-old was the lowest. The expressions of Smads gene of ram in the 2-day-old was higher than ewe, and the expressions of Smad2, Smad4, and Smad7 genes of ram in 2-month-old and 6-month-old were lower than the ewe in 2-day-old, the expression of Smad3 gene of ram in 3 growth stages were higher than ewe. The correlation expression of Smads gene and YAP1 gene in TGF-β/smad signaling of sheep muscle was found that there was no significant correlation in 2-day-old of gastrocnemius muscle between YAP1 and smads (P>0.05) . The expression between YAP1 and Smad2 had a significant positive correlation (P<0.05) and the correlation of the expression between YAP1 and other Smads was not significant in 2-month-old of gastrocnemius muscle (P>0.05). There was a significant negative correlation between YAP1 and Smad3 in different growth stages of gastrocnemius muscle(P<0.01). YAP1 expression exhibited a high positive correlation with Smad3 and the expression of YAP1 with the others was significantiy correlated in extensor digitorum longus of 2-month-old (P<0.05). There was no significant correlation between YAP1 and Smads in 2-month-old of extensor digitorum longus (P>0.05). The expression between YAP1 and Smad7 had a high significant positive correlation (P<0.01) and the correlation of expression between YAP1 and other Smads was not significant in 6-month-old of extensor digitorum longus (P>0.05). There were highly significant negative correlations between YAP1 and Smads in different growth stages of extensor digitorum longus (P<0.01). 【Conclusion】 It was suggested that different tissues, growth stages and gender could affect the expression of Smads in muscle. YAP1 of Hippo pathway may participate in regulating the TGF-β/smad pathway and the process of muscle proliferation and differentiation in gastrocnemius muscle and extensor digitorum longus of Hu sheep.

Key words: Hu sheep, Smads, YAP1, Hippo pathway, TGF-&beta, pathway

[1]    OVERHOLTZER M, ZHANG J, SMOLEN G A, MUIR B, LI W, SGROI D C, DENG C X, BRUGGE J S, HABER D A. Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(33):12405-12410.
[2]    史梦婕, 邵松军, 李洁媚, 周艳芳, 黄培春. Hippo通路与肿瘤相关性研究进展. 中国细胞生物学学报, 2014, 36(3):361-365.
SHI M J, SHAO S J, LI J M, ZHOU Y F, HUANG P C. The advances in Hippo pathway association with cancer. Chinese Journal of Cell Biology, 2014, 36(3):361-365.(in Chinese)
[3]    张靖, 朱金水. Hippo-YAP信号通路与胃癌相关性研究. 国际消化病杂志, 2011, 31(4):207-215.
ZHANG J, ZHU J S. The advances in Hippo signaling pathway association with gastric cancer. International Journal of Digestive Disease, 2011, 31(4):207-215.(in Chinese)
[4]    NGUYEN L T, TRETIAKOVA M S, SILVIS M R, LUCAS J, KLEZOVITCH O, COLEMAN I, BOLOURI H, KUTYAVIN V I, MORRISSEY C, TRUE L D, NELSON P S, VASIOUKHIN V. ERG activates the YAP1 transcriptional program and induces the development of age-related prostate tumors. Cancer Cell, 2015, 27(6):797-808.
[5]    MELFI S, COLCIAGO A, GIANNOTTI G, BONALUME V, CAFFINO L, FUMAGALLI F, MAGNAGHI V. Stressing out the Hippo/YAP signaling pathway: toward a new role in Schwann cells. Cell Death and Disease, 2015, 6:e1915. doi: 10.1038/cddis.2015.291.
[6]    CAO X, PFAFF S L, GAGE F H. YAP regulates neural progenitor cell number via the TEA domain transcription factor. Genes and Development, 2008, 22(23):3320-3334.
[7]    PLOUFFE S W, HONG A W, GUAN K L. Disease implications of the Hippo/YAP pathway. Trends in Molecular Medicine, 2015, 21(4): 212-222.
[8]    MOUSTAKAS A, SOUCHELNYTSKYI S, HELDIN C H. Smad regulation in TGF-beta signal transduction. Journal of Cell Science, 2001, 114(Pt 24):4359-4369.
[9]    XU P, LIU J, DERYNCK R. Post-translational regulation of TGF-β receptor and Smad signaling. Febs Letters, 2012, 586(14):1871-1884.
[10]   MOUSTAKAS A, HELDIN C H. The regulation of TGFbeta signal transduction. Development, 2009, 136(22):3699-3714.
[11]   WAKEFIELD L M, HILL C S. Beyond TGFβ: roles of other TGFβ superfamily members in cancer. Nature Reviews Cancer, 2013, 13(5): 328-341.
[12]   IKUSHIMA H, MIYAZONO K. TGFbeta signalling: a complex web in cancer progression. Nature Reviews Cancer, 2010, 10(6):415-424.
[13]   YAN X, LIAO H, CHENG M, SHI X, LIN X, FENG X H, CHEN Y G. Smad7 protein interacts with Receptor regulated Smads (R-Smads)- Smads to inhibit transforming growth factor-β(TGF-β)/Smad signaling. Journal of Biological Chemistry, 2016, 291: 382-392.
[14]   LÖNN P, MORÉN A, RAJA E, DAHL M, MOUSTAKAS A. Regulating the stability of TGFbeta receptors and Smads. Cell Research, 2009, 19(1):21-35.
[15]   FERRIGNO O, LALLEMAND F, VERRECCHIA F, L'HOSTE S, CAMONIS J, ATFI A, MAUVIEL A. Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-β/Smad signaling. Oncogene, 2002, 21(32):4879-4884.
[16]   SCHILD L, LU Y, GAUTSCHI I, SCHNEEBERGER E, LIFTON R  P, ROSSIER B C. Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome. EMBO Journal, 1996, 15(10): 2381-2387.
[17]   孙伟, 李达, 苏锐, 马月辉, 关伟军, 张有法, 陈玲, 吴文忠, 周洪. 绵羊YAP1 基因全长cDNA 克隆及生物信息学分析. 中国农业科学, 2013, 46(8):1725-1735.
SUN W, LI D, SU R, MA Y H, GUAN W J, ZHANG Y F, CHEN L, WU W Z, ZHOU H. Cloning and bioinformatics analysis of full- length cDNA sequence of YAP1 gene in sheep. Scientia Agricultura Sinica, 2013, 46(8):1725-1735.(in Chinese)
[18]   KOLLIAS H D, MCDERMOTT J C. Transforming growth factor-beta and myostatin signaling in skeletal muscle. Journal of Applied Physiology, 2008, 104(3):579-587.
[19]   NAKAMURA R, KAYAMORI K, OUE E, SAKAMOTO K, HARADA K, YAMAGUCHI A. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma. Biochemical and Biophysical Research Communications, 2015, 458(4):777-782.
[20]   FUJII M, TOYODA T, NAKANISHI H, YATABE Y, SATO A, MATSUDAIRA Y, ITO H, MURAKAMI H, KONDO Y, KONDO E, HIDA T, TSUJIMURA T, OSADA H, SEKIDO Y. TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth. Journal of Experimental Medicine, 2012, 209(3): 479-494.
[21]   NAKAO A, AFRAKHTE M, MORÉN A, NAKAYAMA T, CHRISTIAN J L, HEUCHEL R, ITOH S, KAWABATA M, HELDIN N E, HELDIN C H, TEN DIJKE P. Identification of Smad7, a TGF beta-inducible antagonist of TGF-beta signaLling. Nature, 1997, 389(6651):631-635.
[22]   BEPPU H. Smad7-modified alleles by various gene-targeting strategies. Journal of Biochemistry, 2013, 153(5):399-401.
[23]   DROGUETT R, CABELLO-VERRUGIO C, SANTANDER C, BRANDAN E. TGF-beta receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation. Experimental Cell Research, 2010, 316(15):2487-2503.
[24]   FOURNIER P G, JUÁREZ P, JIANG G, CLINES G A, NIEWOLNA M, KIM H S, WALTON H W, PENG X H, LIU Y, MOHAMMAD K S, WELLS C D, CHIRGWIN J M, GUISE T A. The TGF-β signaling regulator PMEPA1 suppresses prostate cancer metastases to bone. Cancer Cell, 2015, 27(6):809-821.
[25]   NAKAO A, IMAMURA T, SOUCHELNYTSKYI S, KAWABATA M, ISHISAKI A, OEDA E, TAMAKI K, HANAI J, HELDIN CH, MIYAZONO K, TEN DIJKE P. TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO Journal, 1997, 16(17): 5353-5362.
[26]   徐业芬. Smad信号转导通路相关基因表达与湖羊高繁殖力关系的研究[D]. 南京: 南京农业大学, 2010.
XU Y F. Gene expressions related to smad sigenaling molecule and its relationship with fecundity in Hu sheep[D]. Nanjing: Nanjing Agricultural University, 2010.(in Chinese)
[27]   GOLDSTEIN J A, BOGDANOVICH S, BEIRIGER A, WREN L M, ROSSI A E, GAO Q Q, GARDNER B B, EARLEY J U, MOLKENTIN J D, MCNALLY E M. Excess SMAD signaling contributes to heart and muscle dysfunction in muscular dystrophy. Human Molecular Genetics, 2014, 23(25):6722-6731.
[28]   COHEN T V, KOLLIAS H D, LIU N, WARD C W, WAGNER K R. Genetic disruption of Smad7 impairs skeletal muscle growth and regeneration. Journal of Physiology, 2015, 593(11):2479-2497.
[29]   GUO J, KLEEFF J, ZHAO Y, LI J, GIESE T, ESPOSITO I, BÜCHLER M W, KORC M, FRIESS H. Yes-associated protein (YAP65) in relation to Smad7 expression in human pancreatic ductal adenocarcinoma. International Journal of Molecular Medicine, 2006, 17(5):761-767.
[30]   SUN J G, CHEN X W, ZHANG L P, WANG J, DIEHN M. Yap1 promotes the survival and self-renewal of breast tumor initiating cells via inhibiting Smad3 signaling. Oncotarget, 2015, doi: 10.18632/ oncotarget.6655.
[1] MA YaMei,ZHANG ShaoHong,ZHAO JunLiang,LIU Bin. Function of FCS-Like Zinc-Finger Protein OsFLZ18 in Regulating Rice Flowering Time [J]. Scientia Agricultura Sinica, 2022, 55(20): 3875-3884.
[2] ChunTao ZHANG,Tao MA,Yan TU,QiYu DIAO. Effects of Circadian Rhythm on Rumen Fermentation and Nutrient Digestion of Mutton Sheep [J]. Scientia Agricultura Sinica, 2022, 55(18): 3664-3674.
[3] LI WenJuan,TAO Hui,ZHANG NaiFeng,MA Tao,DIAO QiYu. Effects of High-Fat Diet on Energy Metabolism and Slaughter Performance of Early-Weaning Lambs [J]. Scientia Agricultura Sinica, 2021, 54(10): 2206-2216.
[4] ZHANG DeYin,ZHANG XiaoXue,LI FaDi,LI Chong,LI GuoZe,ZHANG YuKun,LI XiaoLong,SONG QiZhi,ZHAO Yuan,LIU XiaoQing,MA LiangQiang,WANG WeiMin. Association of Rumen Histomorphology of Sheep with Different Feed Efficiencies [J]. Scientia Agricultura Sinica, 2020, 53(24): 5115-5124.
[5] CHAI JianMin, WANG Bo, QI MinLi, WANG ShiQin, TU Yan, TAO XiaoJing, DIAO QiYu, ZHANG NaiFeng. Effect of Weaning Liquid Diet at Different Level of Creep Feed Intake on Growth and Development of Lambs [J]. Scientia Agricultura Sinica, 2018, 51(2): 341-350.
[6] JIN ChengYan, Lü XiaoYang, GAO Wen, WANG Yue, CHEN WeiHao, SHENG ShuiXing, CHEN Ling, LIN Jie, SUN Wei. Study on the Relationship Between the Expression of Candidate miRNAs and the Developmental Characteristics in Different Patterns in Hu Sheep Lambskin [J]. Scientia Agricultura Sinica, 2018, 51(14): 2814-2824.
[7] QIN Yu-hai, ZHANG Xiao-hong, FENG Lu, LI Wei-wei, XU Zhao-shi, LI Lian-cheng, ZHOU Yong-bin, MA You-zhi, DIAO Xian-min, JIA Guan-qing, CHEN Ming, MIN Dong-hong. Response of Millet Transcription Factor Gene SibZIP42 to High Salt and ABA Treatment in Transgenic Arabidopsis [J]. Scientia Agricultura Sinica, 2016, 49(17): 3276-3286.
[8] JIA Xiao-yun, JIN Lei-hao, MIAO Lian-juan, DING Na, FAN Rui-wen, DONG Chang-sheng. Melanin Synthesis of Alpaca Melanocytes Regulated by miR-663 Through Targeting TGF-β1 [J]. Scientia Agricultura Sinica, 2015, 48(1): 165-173.
[9] YIN Jin-Feng-1, NI Rong-1, WANG Qing-Zeng-1, SUN Wei-1, DING Jia-Tong-1, ZHANG You-Fa-2, CHEN Ling-2, WU Wen-Zhong-2, ZHOU Hong-3. The Genetic Polymorphism, Expression of BMP7 Gene and Its Relationship with Lamb Skin Follicle Traits in Hu Sheep [J]. Scientia Agricultura Sinica, 2014, 47(9): 1811-1818.
[10] SUN Wei, LI Da, SU Rui, MA Yue-Hui, GUAN Wei-Jun, ZHANG You-Fa, CHEN Ling, WU Wen-Zhong, ZHOU Hong. Cloning and Bioinformatics Analysis of Full-Length cDNA Sequence of YAP1 Gene in Sheep [J]. Scientia Agricultura Sinica, 2013, 46(8): 1725-1735.
[11] GUO Jing-1, LI Xin-Yu-1, LI Yin-Xia-2, PAN Zeng-Xiang-1, JUE Ken-3, LIU Ji-Ying-1, LI 二Lin-1, XIE Zhuang-1, CHEN Ling-4, LI Qi-Fa-1. Characterization, Expression of TGF-β1 Gene and Its Association with Ovulation Rate in Hu Sheep [J]. Scientia Agricultura Sinica, 2013, 46(21): 4586-4593.
[12] SUN Wei, NI Rong, YIN Jin-Feng, DING Jia-Tong, ZHANG You-Fa, CHEN Ling, WU Wen-Zhong, ZHOU Hong. Screening Differentially Expressed Genes of Skin Tissue of Different Flowers Patterns of Hu Sheep [J]. Scientia Agricultura Sinica, 2013, 46(2): 376-384.
[13] LIAO Fang-Fang, YUAN Si-Chun, ZHANG Zhong-Wen, WU Guo-Juan. Constructions of Arkadia and UCH37 Expression Vectors and Effects on TGF-β1/Smad7 Signal Pathway [J]. Scientia Agricultura Sinica, 2012, 45(9): 1848-1856.
[14] YING Shi-Jia, NIE Hai-Tao, ZHANG Guo-Min, WU Yong-Cong, WANG Zi-Yu, PANG Xun-Sheng, WANG Chang-Long, HE Dong-Yang, JIA Ruo-Xin, WANG Feng. Effects of Different Levels of Diet on Plasma Physiochemical Indexes and Folliculogenesis in Hu Sheep During the Luteal Phase [J]. Scientia Agricultura Sinica, 2012, 45(8): 1606-1612.
[15] SUN Wei, LI Da, MA Yue-Hui, GUAN Wei-Jun, CHU Ming-Xing, DING Jia-Tong, LI Bi-Chun, ZHANG You-Fa, CHEN Ling, WU Wen-Zhong, ZHOU Hong. Developmental Changes of Gene Expression of GHR and IGF-Ⅰ Genes and Their Association Analysis with Meat Quality Traits in Hu Sheep [J]. Scientia Agricultura Sinica, 2012, 45(22): 4678-4687.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!