[논문]Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor

Wu, Tianyi; Qi, Wenxiao; Shan, Haojie; Tu, Bin; Jiang, Shilin; Lu, Ye; Wang, Feng

doi:10.1016/j.jgr.2021.08.005

Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor 원문보기

Journal of ginseng research = 高麗人參學會誌, v.46 no.4, 2022년, pp.526 - 535

Wu, Tianyi (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) , Qi, Wenxiao (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) , Shan, Haojie (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) , Tu, Bin (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) , Jiang, Shilin (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) , Lu, Ye (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) , Wang, Feng (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital)

Abstract ▼ AI-Helper

Background: During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. Methods: In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Results: Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Conclusion: Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

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표/그림 (5)

그림 Fig. 1. Impact of Rg1 on histology, matrix-related factors and function of tendon in AT rat model. (A) H&E staining of tendon tissues in AT rat model at 8 weeks post-surgery. Scale bar, 100 μm. (B) Expression of COL1a1, COL3a1, DCN, and TNC were measured by qRT-PCR. (C) Hydroxyproline content in tendon tissues of each group. (D) Expression of SCX, MKX, and TNMD were measured by qRT-PCR. (E-F) Stiffness and tensile strength of tendon tissues in each group. COL, collagen. DCN, decorin. TNC, tenascin-C. Scleraxis, SCX. Mohawk, MKX. Tenomodulin, TNMD. AT, Achilles tendinitis. Data were presented as means ± SD. n = 7-9. *P < 0.05, **P < 0.01, ***P < 0.001 versus control group. &P < 0.05, &&P < 0.01 versus AT group. #P < 0.05, ##P < 0.01.
그림 Fig. 2. The impacts of Rg1 on tendon inflammation. (A) The mRNA levels of pro-inflammatory factors COX-2, IL-1β, IL-6, and TNF-α in tendon tissues were evaluated by qRT-PCR at 3 weeks post-surgery. (B) The mRNA levels of anti-inflammatory factors IL-4 and IL-10 were assessed by qRT-PCR. (C) The mRNA levels of MMP-3 and MMP-9 were evaluated by qRTPCR. (D-E) Expression of apoptosis-related proteins were detected by western blotting. Quantitative analysis was also performed. Data were presented as means ± SD. n = 6. *P < 0.05, **P < 0.01, ***P < 0.001 versus control group. &P < 0.05, &&P < 0.01 versus AT group. #P < 0.05.
그림 Fig. 3. Rg1 significantly promotes the proliferation and migration of tenocytes. (A) The proliferation of tenocytes after Rg1 treatment was measured by EdU assays. Scale bar, 50 μm. The migration ability of tenocytes after Rg1 treatment was measured by transwell assay (B) (Scale bar, 50 μm) and scratch test assay (C) (Scale bar, 100 μm). (D, E) Rg1 protected tenocytes against H₂O₂-induced apoptosis. (F) mRNA levels of SCX, MKX, and TNMD in tenocytes were measured by qRT-PCR. Data were presented as means ± SD. n = 6 (technical replicates). Experiments were independently performed for at least 3 times. *P < 0.05, **P < 0.01, ***P < 0.001 versus control group. &P < 0.05, &&P < 0.01 versus H₂O₂ group. #P < 0.05.
그림 Fig. 4. Rg1 promotes the proliferation and migration of tenocytes via ER. (A) The proliferation of tenocytes after Rg1 and ICI182780 treatment was measured by EdU assays. Scale bar, 50 μm. The migration ability of tenocytes after Rg1 and ICI182780 treatment was measured by transwell assay (B) (Scale bar, 50 μm) and scratch test assay (C) (Scale bar, 100 μm). Data were presented as means ± SD. n = 6 (technical replicates). Experiments were independently performed for at least 3 times. *P < 0.05, **P < 0.01versus control group. &P < 0.05 for comparison between Rg1 and Rg1 plus ICI182780 group.
그림 Fig. 5. Ginsenoside Rg1 activated the IGF1R and MAPK signaling pathway through ER. (A-B) Phosphorylated IGF1R at Tyr1135 and Tyr980, phosphorylated Akt and phosphorylated ERK1/2 in tenocytes after Rg1 treatment were detected by western blotting. The quantitative analysis of western blotting was also shown. (C-D) Phosphorylated IGF1R at Tyr1135 and Tyr980, phosphorylated Akt and phosphorylated ERK1/2 in tenocytes after Rg1 and ICI182780 treatment were detected. The quantitative analysis of Western blots is also shown. Data were presented as means ± SD. Experiments were independently performed for at least 3 times. *P < 0.05, **P < 0.01versus control group. &P < 0.05, &&P < 0.01 for comparison between Rg1 and Rg1 plus ICI182780 group.

참고문헌 (63)

1 Choi H.J. Choi S. Kim J.G. Song M.H. Shim K.S. Lim Y.M. Kim H.J. Park K. Kim S.E. Enhanced tendon restoration effects of anti-inflammatory, lactoferrin-immobilized, heparin-polymeric nanoparticles in an Achilles tendinitis rat model Carbohydr Polym 241 2020 116284 10.1016/j.carbpol.2020.116284 32507170

상세보기
2 Liu Y.C. Wang H.L. Huang Y.Z. Weng Y.H. Chen R.S. Tsai W.C. Yeh T.H. Lu C.S. Chen Y.L. Lin Y.W. Chen Y.J. Hsu C.C. Chiu C.H. Chiu C.C. Alda-1, an activator of ALDH2, ameliorates Achilles tendinopathy in cellular and mouse models Biochem Pharmacol 175 2020 113919 10.1016/j.bcp.2020.113919 32194057

상세보기
3 Lipman K. Wang C. Ting K. Soo C. Zheng Z. Tendinopathy: injury, repair, and current exploration Drug Des Dev Ther 12 2018 591 603 10.2147/DDDT.S154660

상세보기
4 Docheva D. Muller S.A. Majewski M. Evans C.H. Biologics for tendon repair Adv Drug Deliv Rev 84 2015 222 239 10.1016/j.addr.2014.11.015 25446135

상세보기
5 Bian X. Liu T. Yang M. Gu C. He G. Zhou M. Tang H. Lu K. Lai F. Wang F. Yang Q. Gustafsson J.A. Fan X. Tang K. The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis J Cell Mol Med 24 2020 9925 9935 10.1111/jcmm.15592 32776630

상세보기
6 Gonzalez-Quevedo D. Diaz-Ramos M. Chato-Astrain J. Sanchez-Porras D. Tamimi I. Campos A. Campos F. Carriel V. Improving the regenerative microenvironment during tendon healing by using nanostructured fibrin/agarose-based hydrogels in a rat Achilles tendon injury model Bone Joint Lett J 102-B 2020 1095 1106 10.1302/0301-620X.102B8.BJJ-2019-1143.R2

상세보기
7 Zhang M. Liu H. Cui Q. Han P. Yang S. Shi M. Zhang T. Zhang Z. Li Z. Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon Stem Cell Res Ther 11 2020 402 10.1186/s13287-020-01918-x 32943109

상세보기
8 Yu J.-s. Jin J. Li Y.-y. The Physiological functions of IKK-selective substrate identification and their critical roles in diseases STEMedicine 1 2020 e49 10.37175/stemedicine.v1i4.49
9 Wang Y. He G. Tang H. Shi Y. Kang X. Lyu J. Zhu M. Zhou M. Yang M. Mu M. Chen W. Zhou B. Zhang J. Tang K. Aspirin inhibits inflammation and scar formation in the injury tendon healing through regulating JNK/STAT-3 signalling pathway Cell Prolif 52 2019 e12650 10.1111/cpr.12650

상세보기
10 Leblanc D.R. Schneider M. Angele P. Vollmer G. Docheva D. The effect of estrogen on tendon and ligament metabolism and function J Steroid Biochem Mol Biol 172 2017 106 116 10.1016/j.jsbmb.2017.06.008 28629994

상세보기
11 Hansen M. Kjaer M. Sex hormones and tendon Adv Exp Med Biol 920 2016 139 149 10.1007/978-3-319-33943-6_13 27535256
12 Nogara P.R.B. Godoy-Santos A.L. Fonseca F.C.P. Cesar-Netto C. Carvalho K.C. Baracat E.C. Maffulli N. Pontin P.A. Santos M.C.L. Association of estrogen receptor beta polymorphisms with posterior tibial tendon dysfunction Mol Cell Biochem 471 2020 63 69 10.1007/s11010-020-03765-z 32472323

상세보기
13 Bian X. Liu T. Zhou M. He G. Ma Y. Shi Y. Wang Y. Tang H. Kang X. Yang M. Gustafsson J.A. Fan X. Tang K. Absence of estrogen receptor beta leads to abnormal adipogenesis during early tendon healing by an up-regulation of PPARgamma signalling J Cell Mol Med 23 2019 7406 7416 10.1111/jcmm.14604 31475784

상세보기
14 Cheng W. Jing J. Wang Z. Wu D. Huang Y. Chondroprotective effects of ginsenoside Rg1 in human osteoarthritis chondrocytes and a rat model of anterior cruciate ligament transection Nutrients 9 2017 10.3390/nu9030263

상세보기
15 Gao Q.G. Chan H.Y. Man C.W. Wong M.S. Differential ERalpha-mediated rapid estrogenic actions of ginsenoside Rg1 and estren in human breast cancer MCF-7 cells J Steroid Biochem Mol Biol 141 2014 104 112 10.1016/j.jsbmb.2014.01.014 24508513

상세보기
16 Komatsu I. Wang J.H. Iwasaki K. Shimizu T. Okano T. The effect of tendon stem/progenitor cell (TSC) sheet on the early tendon healing in a rat Achilles tendon injury model Acta Biomater 42 2016 136 146 10.1016/j.actbio.2016.06.026 27329787

상세보기
17 Yu H. Zhen J. Yang Y. Du J. Leng J. Tong Q. Rg1 protects H9C2 cells from high glucose-/palmitate-induced injury via activation of AKT/GSK-3 beta/Nrf 2 pathway J Cell Mol Med 24 2020 8194 8205 10.1111/jcmm.15486 32548942

상세보기
18 Luo M. Yan D. Sun Q. Tao J. Xu L. Sun H. Zhao H. Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF-kB/NLRP3 pathway J Cell Biochem 121 2020 2994 3004 10.1002/jcb.29556 31709615

상세보기
19 Wu Y.F. Huang Y.T. Wang H.K. Yao C.J. Sun J.S. Chao Y.H. Hyperglycemia augments the adipogenic transdifferentiation potential of tenocytes and is alleviated by cyclic mechanical stretch Int J Mol Sci 19 2017 10.3390/ijms19010090

상세보기
20 Ito Y. Toriuchi N. Yoshitaka T. Ueno-Kudoh H. Sato T. Yokoyama S. Nishida K. Akimoto T. Takahashi M. Miyaki S. Asahara H. The Mohawk homeobox gene is a critical regulator of tendon differentiation Proc. Natl. Acad. Sci. U.S.A 107 2010 10538 10542 10.1073/pnas.1000525107 20498044

상세보기
21 Mendias C.L. Gumucio J.P. Bakhurin K.I. Lynch E.B. Brooks S.V. Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts J Orthop Res 30 2012 606 612 10.1002/jor.21550 21913219

상세보기
22 Voleti P.B. Buckley M.R. Soslowsky L.J. Tendon healing: repair and regeneration Annu Rev Biomed Eng 14 2012 47 71 10.1146/annurev-bioeng-071811-150122 22809137

상세보기
23 Bai L. Gao J. Wei F. Zhao J. Wang D. Wei J. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes Front Pharmacol 9 2018 423 10.3389/fphar.2018.00423 29765322

상세보기
24 Alolga R.N. Nuer-Allornuvor G.F. Kuugbee E.D. Yin X. Ma G. Ginsenoside Rg1 and the control of inflammation implications for the therapy of type 2 diabetes: a review of scientific findings and call for further research Pharmacol Res 152 2020 104630 10.1016/j.phrs.2020.104630 31911245

상세보기
25 Shi D.D. Huang Y.H. Lai C.S.W. Dong C.M. Ho L.C. Li X.Y. Wu E.X. Li Q. Wang X.M. Chen Y.J. Chung S.K. Zhang Z.J. Ginsenoside Rg1 prevents chemotherapy-induced cognitive impairment: associations with microglia-mediated cytokines, neuroinflammation, and neuroplasticity Mol Neurobiol 56 2019 5626 5642 10.1007/s12035-019-1474-9 30659419

상세보기
26 Yang G. Rothrauff B.B. Tuan R.S. Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm Birth Defects Res C Embryo Today 99 2013 203 222 10.1002/bdrc.21041 24078497

상세보기
27 Lin T.W. Cardenas L. Soslowsky L.J. Biomechanics of tendon injury and repair J Biomech 37 2004 865 877 10.1016/j.jbiomech.2003.11.005 15111074

상세보기
28 Fenwick S.A. Hazleman B.L. Riley G.P. The vasculature and its role in the damaged and healing tendon Arthritis Res 4 2002 252 260 10.1186/ar416 12106496
29 Thankam F.G. Roesch Z.K. Dilisio M.F. Radwan M.M. Kovilam A. Gross R.M. Agrawal D.K. Association of inflammatory responses and ECM disorganization with HMGB1 upregulation and NLRP3 inflammasome activation in the injured rotator cuff tendon Sci Rep 8 2018 8918 10.1038/s41598-018-27250-2 29891998

상세보기
30 Freedman B.R. Rodriguez A.B. Leiphart R.J. Newton J.B. Ban E. Sarver J.J. Mauck R.L. Shenoy V.B. Soslowsky L.J. Dynamic loading and tendon healing affect multiscale tendon properties and ECM stress transmission Sci Rep 8 2018 10854 10.1038/s41598-018-29060-y 30022076

상세보기
31 Fu S.C. Hung L.K. Shum W.T. Lee Y.W. Chan L.S. Ho G. Chan K.M. In vivo low-intensity pulsed ultrasound (LIPUS) following tendon injury promotes repair during granulation but suppresses decorin and biglycan expression during remodeling J Orthop Sports Phys Ther 40 2010 422 429 10.2519/jospt.2010.3254 20479531

상세보기
32 Yoon J.H. Halper J. Tendon proteoglycans: biochemistry and function J Musculoskelet Neuronal Interact 5 2005 22 34 15788868
33 Jarvinen T.A. Kannus P. Jarvinen T.L. Jozsa L. Kalimo H. Jarvinen M. Tenascin-C in the pathobiology and healing process of musculoskeletal tissue injury Scand J Med Sci Sports 10 2000 376 382 10.1034/j.1600-0838.2000.010006376.x 11085568

상세보기
34 Nayak B.S. Kanhai J. Milne D.M. Pinto Pereira L. Swanston W.H. Experimental evaluation of ethanolic extract of Carapa guianensis L. Leaf for its wound healing activity using three wound models Evid base Compl Alternative Med 2011 2011 419612 10.1093/ecam/nep160

상세보기
35 Langberg H. Boushel R. Skovgaard D. Risum N. Kjaer M. Cyclo-oxygenase-2 mediated prostaglandin release regulates blood flow in connective tissue during mechanical loading in humans J Physiol 551 2003 683 689 10.1113/jphysiol.2003.046094 12813143

상세보기
36 Millar N.L. Wei A.Q. Molloy T.J. Bonar F. Murrell G.A. Cytokines and apoptosis in supraspinatus tendinopathy J Bone Joint Surg 91 2009 417 424 10.1302/0301-620X.91B3.21652

상세보기
37 Lake J.E. Ishikawa S.N. Conservative treatment of Achilles tendinopathy: emerging techniques Foot Ankle Clin 14 2009 663 674 10.1016/j.fcl.2009.07.003 19857840

상세보기
38 Schulze-Tanzil G. Al-Sadi O. Wiegand E. Ertel W. Busch C. Kohl B. Pufe T. The role of pro-inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights Scand J Med Sci Sports 21 2011 337 351 10.1111/j.1600-0838.2010.01265.x 21210861

상세보기
39 Vincenti M.P. The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression Methods Mol Biol 151 2001 121 148 10.1385/1-59259-046-2:121 11217296

상세보기
40 Egerbacher M. Arnoczky S.P. Caballero O. Lavagnino M. Gardner K.L. Loss of homeostatic tension induces apoptosis in tendon cells: an in vitro study Clin Orthop Relat Res 466 2008 1562 1568 10.1007/s11999-008-0274-8 18459026

상세보기
41 Chuen F.S. Chuk C.Y. Ping W.Y. Nar W.W. Kim H.L. Ming C.K. Immunohistochemical characterization of cells in adult human patellar tendons J Histochem Cytochem 52 2004 1151 1157 10.1369/jhc.3A6232.2004 15314082

상세보기
42 Inoue S. Browne G. Melino G. Cohen G.M. Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway Cell Death Differ 16 2009 1053 1061 10.1038/cdd.2009.29 19325570

상세보기
43 Kim Y.M. Jin J.J. Lee S.J. Seo T.B. Ji E.S. Treadmill exercise with bone marrow stromal cells transplantation facilitates neuroprotective effect through BDNF-ERK1/2 pathway in spinal cord injury rats J Exerc Rehabil 14 2018 335 340 10.12965/jer.1836264.132 30018915

상세보기
44 Chen Q. Liang Q. Zhuang W. Zhou J. Zhang B. Xu P. Ju Y. Morita Y. Luo Q. Song G. Tenocyte proliferation and migration promoted by rat bone marrow mesenchymal stem cell-derived conditioned medium Biotechnol Lett 40 2018 215 224 10.1007/s10529-017-2446-7 29018992

상세보기
45 Clegg D.J. Minireview: the year in review of estrogen regulation of metabolism Mol Endocrinol 26 2012 1957 1960 10.1210/me.2012-1284 23051593

상세보기
46 Kato M. Takaishi H. Yoda M. Tohmonda T. Takito J. Fujita N. Hosogane N. Horiuchi K. Kimura T. Okada Y. Saito T. Kawaguchi H. Kikuchi T. Matsumoto M. Toyama Y. Chiba K. GRIP1 enhances estrogen receptor alpha-dependent extracellular matrix gene expression in chondrogenic cells Osteoarthritis Cartilage 18 2010 934 941 10.1016/j.joca.2010.03.008 20346402

상세보기
47 Dey P. Strom A. Gustafsson J.A. Estrogen receptor beta upregulates FOXO3a and causes induction of apoptosis through PUMA in prostate cancer Oncogene 33 2014 4213 4225 10.1038/onc.2013.384 24077289

상세보기
48 Chan R.Y. Chen W.F. Dong A. Guo D. Wong M.S. Estrogen-like activity of ginsenoside Rg1 derived from Panax notoginseng J Clin Endocrinol Metab 87 2002 3691 3695 10.1210/jcem.87.8.8717 12161497

상세보기
49 Shi C. Zheng D.D. Fang L. Wu F. Kwong W.H. Xu J. Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt Biochim Biophys Acta 1820 2012 453 460 10.1016/j.bbagen.2011.12.005 22178929

상세보기
50 Chen W.F. Lau W.S. Cheung P.Y. Guo D.A. Wong M.S. Activation of insulin-like growth factor I receptor-mediated pathway by ginsenoside Rg1 Br J Pharmacol 147 2006 542 551 10.1038/sj.bjp.0706640 16415910

상세보기
51 Chen W.F. Zhou L.P. Chen L. Wu L. Gao Q.G. Wong M.S. Involvement of IGF-I receptor and estrogen receptor pathways in the protective effects of ginsenoside Rg1 against Abeta(2)(5)(-)(3)(5)-induced toxicity in PC12 cells Neurochem Int 62 2013 1065 1071 10.1016/j.neuint.2013.03.018 23603302

상세보기
52 Lau W.S. Chan R.Y. Guo D.A. Wong M.S. Ginsenoside Rg1 exerts estrogen-like activities via ligand-independent activation of ERalpha pathway J Steroid Biochem Mol Biol 108 2008 64 71 10.1016/j.jsbmb.2007.06.005 17936617

상세보기
53 Lau W.S. Chen W.F. Chan R.Y. Guo D.A. Wong M.S. Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells Br J Pharmacol 156 2009 1136 1146 10.1111/j.1476-5381.2009.00123.x 19298253

상세보기
54 Ishihara H. Sasaoka T. Wada T. Ishiki M. Haruta T. Usui I. Iwata M. Takano A. Uno T. Ueno E. Kobayashi M. Relative involvement of Shc tyrosine 239/240 and tyrosine 317 on insulin induced mitogenic signaling in rat 1 fibroblasts expressing insulin receptors Biochem Biophys Res Commun 252 1998 139 144 10.1006/bbrc.1998.9621 9813159

상세보기
55 Ravichandran K.S. Signaling via Shc family adapter proteins Oncogene 20 2001 6322 6330 10.1038/sj.onc.1204776 11607835

상세보기
56 Song R.X. Barnes C.J. Zhang Z. Bao Y. Kumar R. Santen R.J. The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane Proc. Natl. Acad. Sci. U.S.A 101 2004 2076 2081 10.1073/pnas.0308334100 14764897

상세보기
57 Gao Q.G. Zhou L.P. Lee V.H. Chan H.Y. Man C.W. Wong M.S. Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway J Ginseng Res 43 2019 527 538 10.1016/j.jgr.2018.03.004 31695561

원문보기 상세보기
58 Greger J.G. Guo Y. Henderson R. Ross J.F. Cheskis B.J. Characterization of MNAR expression Steroids 71 2006 317 322 10.1016/j.steroids.2005.09.016 16297421

상세보기
59 Cookman C.J. Belcher S.M. Estrogen receptor-beta up-regulates IGF1R expression and activity to inhibit apoptosis and increase growth of medulloblastoma Endocrinology 156 2015 2395 2408 10.1210/en.2015-1141 25885794

상세보기
60 Disser N.P. Sugg K.B. Talarek J.R. Sarver D.C. Rourke B.J. Mendias C.L. Insulin-like growth factor 1 signaling in tenocytes is required for adult tendon growth FASEB (Fed Am Soc Exp Biol) J 33 2019 12680 12695 10.1096/fj.201901503R

상세보기
61 Haramoto Y. Takahashi S. Oshima T. Onuma Y. Ito Y. Asashima M. Insulin-like factor regulates neural induction through an IGF1 receptor-independent mechanism Sci Rep 5 2015 11603 10.1038/srep11603 26112133

상세보기
62 Rodrigues Alves A.P.N. Fernandes J.C. Fenerich B.A. Coelho-Silva J.L. Scheucher P.S. Simoes B.P. Rego E.M. Ridley A.J. Machado-Neto J.A. Traina F. IGF1R/IRS1 targeting has cytotoxic activity and inhibits PI3K/AKT/mTOR and MAPK signaling in acute lymphoblastic leukemia cells Canc Lett 456 2019 59 68 10.1016/j.canlet.2019.04.030

상세보기
63 Liang F. Hua J.X. Absorption profiles of sanchinoside R1 and ginsenoside Rg1 in the rat intestine Eur J Drug Metab Pharmacokinet 30 2005 261 268 10.1007/BF03190630 16435571

상세보기

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저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

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