成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	陳柏升 Chen, Po-Sheng
論文名稱：	C型凝集素穿膜蛋白在心血管疾病重要性之探討 The Significance of C-type Transmembrane Protein in Cardiovascular Diseases
指導教授：	劉秉彥 Liu, Ping-Yen 李貽恆 Li, Yi-Heng
學位類別：	博士 Doctor
系所名稱：	醫學院 - 臨床醫學研究所 Institute of Clinical Medicine
論文出版年：	2020
畢業學年度：	108
語文別：	英文
論文頁數：	94
中文關鍵詞：	group 14 C型凝集素穿膜蛋白、內皮拓酸蛋白、凝血酶調節素、心臟再塑形
外文關鍵詞：	C-type lectin domain transmembrane protein group 14, endosialin, thrombomodulin, cardiac remodeling
相關次數：	點閱：71 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

Group 14 C型凝集素(C-type lectin domain)穿膜蛋白的成員包括有內皮拓酸蛋白(endosialin)，凝血酶調節素(thrombomodulin)，CD93及CLEC14A。這些成員在結構上都有其相似處。過去已知內皮拓酸蛋白主要表現在人類及動物發育胚胎的血管組織及纖維細胞中，但在成年動物的血管組織中表現量極少。之後的研究顯示，內皮拓酸蛋白的表現對腫瘤的成長，腫瘤內新生血管的發生與遠端轉移有重要的影響。先前研究雖然也可以發現內皮拓酸蛋白的mRNA可以表現在成年動物的心臟組織中，但是實際內皮拓酸蛋白在心臟組織的表現型態及功能到目前為止則是未知。我們的研究發現在因嚴重心衰竭接受心臟移植手術的病人取出的心臟切片檢體中內皮拓酸蛋白的表現明顯增加。同時，我們也發現培養的心肌細胞及小鼠的心臟在接受刺激後會明顯誘發內皮拓酸蛋白的表現。外加合成的內皮拓酸蛋白則可以刺激培養中的心肌細胞成長，增生，同時也可以抑制doxorubicin誘發之細胞凋亡。外加合成的內皮拓酸蛋白也會影響心肌細胞內肌動蛋白(actin)排列。此外，我們更進一步的發現外加合成的內皮拓酸蛋白可以改善培養中的心肌細胞因接受doxorubicin刺激而受損的收縮功能。另一方面，我們的研究也發現在先天缺少內皮拓酸蛋白的小鼠中，心臟左心室收縮功能比正常小鼠差，心臟中膠原蛋白的含量也比正常小鼠的心臟少。我們的研究結果顯示，內皮拓酸蛋白不只在心臟受刺激後的反應及再塑型有其重要性，同時對正常心臟組織的組成及功能也有扮演其重要的角色。相較於內皮拓酸蛋白，Group 14 C型凝集素(C-type lectin domain)中的另外一個成員，凝血酶調節素，則有較為徹底及廣泛的研究，在許多正常細胞的功能表現及疾病的發生都有其重要性。我們的研究顯示外加合成的凝血酶調節素可以藉由誘發調節AKT/mTOR相關的訊息傳導路徑，有效減少內皮細胞中自噬反應(autophagy)的相關蛋白，進而減少內皮細胞的凋亡。在有粥狀動脈硬化的人體血管組織可以發現，自噬反應相關的細胞標記較沒有粥狀動脈硬化的血管明顯。我們也藉由動物實驗發現，外加合成的凝血酶調節素可以減少缺乏Apo E小鼠的主動脈中自噬反應相關蛋白的表現，同時減少內皮細胞的凋亡，更可以進一步改善血管粥狀動脈硬化的嚴重程度。由我們的研究，可以看出Group 14 C型凝集素對於心血管系統的重要性，不只在於維持正常心血管系統的結構及功能，在心臟或血管受到刺激與傷害後所進行的反應與心臟及血管的再塑型都有其重要性。

C-type (calcium-dependent) lectin domain (CTLD) transmembrane protein group 14 consists of endosialin, thrombomodulin (TM), CD93 and CLEC14A and shares similar characteristics in structure. Normally, endosialin expresses in embryo but less protein expression is detected in adult vasculature. Upregulated endosialin participates in growth, progression, neoangiogenesis and metastasis of tumors. Although mRNA of endosialin could be detected in normal heart tissue, the pattern of protein expression and substantial function of endosialin in heart had never been investigated. Our present study found abundant endosialin expressed in excised heart specimen of end-stage heart failure patients receiving heart transplantation. In addition, our in vitro and in vivo studies found that the expression of endosialin could be activated under different cardiac stresses. We found recombinant endosialin (r-endosialin) stimulated proliferation and growth of H9c2 cells and prohibited doxorubicin induced apoptosis of H9c2 cells. r-Endosialin re-arranged intracellular actin filaments of H9c2 cells into more parallel array and rescued contractile function of beating cardiomyocytes treated with doxorubicin. On the other hand, endosialin deficit mice had worse ventricular systolic function and less collagen content in heart compared to control mice. These results suggested endosialin might play a role in maintenance of normal cardiac structure and functions. In conclusion, our present study demonstrated that the expression of endosialin was induced under certain stimulus and might have significance in maintenance of normal cardiac function and pathological development of cardiac remodeling. In contrast to endosialin, TM is the most well studied member of CTLD group 14. Our present study found that treatment of recombinant TM (rTM) decreased the expression of serum starvation (SS)-induced autophagy-related proteins, and the formation of autophagosomes in endothelial cells (ECs) through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced ECs apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. The findings of our study suggested treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice. In summary, our studies further demonstrated CTLD group 14 proteins are not only crucial in maintenance normal cardiac structure and function but also involved in cardiac and vascular remodeling.

考試合格證明..............................................I
中英文摘要...............................................II
誌謝...................................................VII
目錄....................................................IX
Chapter 1 Introduction...................................1
1 Overview of C-type lectin domain superfamily........1
2 The introduction of endosialin......................2
3 Endosialin participates in tumor growth, progression and metastasis...........................................3
4 Endosialin plays a role in the development of inflammatory and proliferative and fibrotic diseases.....5
5 The significance of endosialin on cardiovascular system: unknown..........................................6
6 The introduction of thrombomodulin..................6
7 The impact of TM on endothelial cellular function...7
8 The purposes of the study...........................8
Chapter 2 The expression of endosialin in heart under cardiac stress..........................................10
1 Background.........................................10
2 Materials and Methods..............................12
2.1 Human cardiac specimens of heart failure........12
2.2 Cell culture....................................12
2.3 Mice............................................12
2.4 Stress experiments..............................13
2.5 Immunohistochemistry assay......................13
2.6 Doxorubicin-induced heart failure and myocardial infarction in mice......................................14
2.7 Immunofluorescence staining assay...............15
2.8 Western blotting assay..........................15
2.9 Statistical analysis............................16
3 Results............................................16
3.1 Endosialin expression in samples from human heart failure.................................................16
3.2 Endosialin was upregulated in mouse with heart failure or myocardial infarction........................16
3.3 The expression of endosialin was induced in cultured cells under stress.............................17
4 Discussion........................................17
Chapter 3 The significance of endosialin on cardiac structure, function and remodeling......................19
1 Background.........................................19
2 Materials and Methods..............................20
2.1 Cell culture....................................20
2.2 Mice............................................20
2.3 Recombinant endosialin protein (r-endosialin)...21
2.4 Cell proliferation assay........................21
2.5 Cell hypertrophy assay..........................21
2.6 Cell apoptosis assay............................22
2.7 Actin filament alignment assay..................22
2.8 Cell contractility assay........................23
2.9 Echocardiography................................24
2.10 Pressure-volume loop analysis..................24
2.11 Western blotting assay.........................24
2.12 Statistical analysis...........................25
3 Results............................................25
3.1 r-Endosialin affected cell behaviors............25
3.2 Cardiac function in endosialin-deficient transgenic mice (endosialinLacZ/LacZ mice)..............26
3.3 Less collagen content detected in endosialin-deficient transgenic mice (endosialinLacZ/LacZ mice)....26
4 Discussion.........................................27
Chapter 4 Autophagy play a role in thrombomodulin-induced protective effect in endothelial cells..................31
1 Background..........................................31
2 Materials and Methods...............................32
2.1 Recombinant TM protein............................32
2.2 Human umbilical vein ECs culture..................33
2.3 Western blot assay................................33
2.4 Autophagosome immunofluorescence staining.........34
2.5 ATG5 knockdown....................................34
2.6 ECs apoptosis assay...............................35
2.7 ECs migration and proliferation assay.............35
2.8 Statistical Analysis..............................36
3 Results.............................................36
3.1 rTM suppresses stress-induced autophagy in cultured ECs.....................................................36
3.2 Autophagy plays a role in rTM effect on ECs.......37
4 Discussion..........................................38
Chapter 5 rTM suppressed autophagy in ECs in vivo and exerted anti-atherosclerotic effect.....................41
1 Background..........................................41
2 Material and Methods................................42
2.1 Immunofluorescent staining of human aortas........42
2.2 ApoE deficient mice...............................42
2.3 Immunofluorescent staining of mouse tissue........43
2.4 Statistical Analysis..............................44
3 Results.............................................44
3.1 Autophagy is activated in intimal ECs in human atherosclerosis.........................................44
3.2 rTM suppresses ECs autophagy activation in apolipoprotein E deficient mice.........................45
4 Discussion..........................................45
Chapter 6 Conclusions and future works..................47
References..............................................75
Publication lists.......................................89
Content of figures.....................................XIV
Abbreviation............................................XV

                                    

Balasubramanian S, Mani SK, Kasiganesan H, Baicu CC, Kuppuswamy D. Hypertrophic stimulation increased ß-actin dynamics in adult feline cardiomyocytes. PLoS One 2010;5:e11470.
Bartis D, Crowley LE, D’Souza VK, Borthwick L, Fisher AJ, Croft AP, Pongrácz JE, Thompson R, Langman G, Buckley CD, Thickett DR. Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis. BMC Pulm Med 2016;16:51.
Borah S, Vasudevan D, Swain RK. C-type lectin family XIV members and angiogenesis. Oncol Lett 2019;18:3954-3962.
Brady J, Neal J, Sadakar N, Gasque P. Human endosialin (tumor endothelial marker 1) is abundantly expressed in highly malignant and invasive brain tumors. J Neuropathol Exp Neurol 2004;63:1274-1283.
Breslow JL. Mouse models of atherosclerosis. Science 1996;272:685-688.
Brown GD, Willment JA, Whitehead L. C-type lectins in immunity and homeostasis. Nat Rev Immunol 2018;18:374-389.
Burchfield JS, Xie M, Hill JA. Pathological ventricular remodeling. Mechanisms: Part 1 of 2. Circulation 2013;128:388-400.
Carlier MF, Pernier J, Montaville P, Shekhar S, Kühn S; Cytoskeleton Dynamcis and Motility group. Control of polarized assembly of actin filaments in cell motility. Cell Mol Life Sci 2015;72:3051-3067.
Carson-Walter EB, Watkins DN, Nanda A, Vogelstein B, Kinzler KW, St. Croix B. Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res 2001;61:6649-6655.
Chao TH, Tsai WC, Chen JY, Liu PY, Chung HC, Tseng SY, Kuo CH, Shi GY, Wu HL, Li YH. Soluble thrombomodulin is a paracrine anti-apoptotic factor for vascular endothelial protection. Int J Cardiol 2014;172:340-349.
Chen G, Zhang W, Li YP, Ren JG, Xu N, Liu H, Wang FQ, Sun ZJ, Jia J, Zhao YF. Hypoxia-induced autophagy in endothelial cells: a double-edged sword in the progression of infantile haemangioma? Cardiovasc Res 2013;98:437-448.
Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med 2013;368:651-662.
Christian S, Ahom H, Eisenhaber F, Rodi HP, Garin-Chesa P, Park JE, Rettig WJ, Lenter MC. Molecular cloning and characterization of endosialin, a C-type lectin-like cell surface receptor of tumor endothelium. J Biol Chem 2001;276:7408-7414.
Christian S, Winkler R, Helfrich I, Boos AM, Besemfelder E, Schadendorf D, Augustin HG. Endosialin (Tem1) is a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. Am J Pathol 2008;172:486-494
Conway EM. Thrombomodulin and its role in inflammation. Semin Immunopathol 2012;34:107-125.
Curtis LH, Whellan DJ, Hammill BG, Hernandez AF, Anstrom KJ, Shea AM, Sxhulman KA. Incidence and prevalence of heart failure in elderly persons, 1994-2003. Arch Intern Med 2008;168:418-424
Davies G, Cunnick GH, Mansel RE, Mason MD, Jiang WG. Levels of expression of endothelial markers specific to tumour-associated endothelial cells and their correlation with prognosis in patients with breast CA. Clin Exp Metastasis 2004;21:31-37.
Dolznig H. Schweifer N, Puri C, Kraut N, Rettig WJ, Kerjaschki D, Garin-Chesa P. Characterization of cancer stroma markers: in silico analysis of an mRNA expression database for fibroblast activation protein and endosialin. Cancer Immun 2005;5:10.
Drickmer K, Fadden AJ. Genomic analysis of C-type lectins. Biochem Soc Symp 2002;69:59-72.
Drickmer K. Evolution of Ca(2+)-dependent animal lectins. Prog Nucleic Acid Res Mol Biol 1993;45:207-232.
Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG, Shi Y. Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol 2012;302:C383-C391.
Eguchi R, Fujimori Y, Okada M, Tamaki H, Wakabayashi I, Ogawa H. Recombinant human soluble thrombomodulin attenuates FK506-induced endothelial dysfunction through prevention of Akt inactivation. Exp Cell Res 2014;323:112-117.
Esmon CT. The regulation of natural anticoagulant pathways. Science 1987;235:1348-1352.
Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989;264:4743-4746.
Fang YH, Wang PH, Gao ZH, Wu SN, Chang HY, Yang PJ, Liu PY, Liu YW. Efficient cardiac differentiation of human amniotic fluid-derived stem cells into induced pluripotent stem cells and their potential immune privilege. Int J Mol Sci 2020;21:2359.
Frangogiannis NG. The extracellular matric in myocardial injury, repair, and remodeling. J Clin Invest 2017;127:1600-1612.
Hasanov Z, Ruckdeschel T, König C, Mogler C, Kapel SS, Korn C, Spegg C, Eichwald V, Wieland M, Appak S, Augustin HG. Endosialin promotes atherosclerosis through phenotypic remodeling of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2017;37:495-505.
Hong YK, Lee YC, Cheng TL, Lai CH, Hsu CK, Kuo CH, Hsu YY, Chang BI, Ma CY, Lin SW, Wang KC, Shi GY, Wu HL. Tumor endothelial marker 1 (TEM1/endosialin/CD248) enhances wound healing by interacting with platelet-derived growth factor receptors. J Invest Dermatol 2019;139:2204-2214.
Hu N, Kong LS, Chen H, Li WD, Qian AM, Wang XY, Du XL, Li CL, Yu XB, Li XQ. Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT. Thromb Res 2015;136:642-651.
Huang HP, Hong CL, Kao CY, Lin SW, Lin SR, Wu HL, Shi GY, You LR, Wu CL, Yu IS. Gene targeting an expression analysis of mouse Tem1/endosialin using a lacZ reporter. Gene Expr Patterns 2011;11:316-326.
Huber MA, Kraut N, Schweifer N, Dolznig H, Peter RU, Schubert RD, Scharffetter-Kochanek K, Pehamberger H, Garin-Chesa P. Expression of stromal cell markers in distinct compartments of human skin cancers. J Cutan Pathol 2006;33:145-155.
Ikezoe T, Yang J, Nishioka C, Honda G, Furihata M, Yokoyama A. Thrombomodulin protects endothelial cells from a calcineurin inhibitor-induced cytotoxicity by upregulation of extracellular signal-regulated kinase/myeloid leukemia cell-1 signaling. Arterioscler Thromb Vasc Biol 2012;32:2259-2270.
Janicki JS, Brower GL. The role of myocardial fibrillar collagen in ventricular remodeling and function. J Card Fail 2002;8:S319-S325.
Khan KA, McMurray JL, Mohammed F, Bicknell R. C-type lectin domain group 14 proteins in vascular biology, cancer and inflammation. FEBS J 2019;286:3299-3332.
Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-141.
Lax S, Hou TZ, Jenkinson E, Salmon M, MacFadyen JR, Isacke CM, Anderson G, Cunningham AF, Buckley CD. CD248/endosialin is dynamically expressed on a subset of stromal cells during lymphoid tissue development, splenic remodeling and repair. FEBS Lett 2007;581:3550-3556.
Lee HC, Shiou YL, Jhuo SJ, Chang CY, Liu PL, Jhuang WJ, Dai ZK, Chen WY, Chen YF, Lee AS. The sodium-glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats. Cardiovasc Diabetol 2019;18:45.
Lesman-Leeqte I, Jaarsma T, Coyne JC, Jillege HL, Van Veldhuiseen DJ, Sanderman R. Quality of life and depressive symptoms in the elderly: a comparison between patients with heart failure and age- and gender-matched community controls. J Card Fail 2009;15:17-23.
Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008;132:27-42.
Li JY, Su CH, Wu YJ, Tien TY, Hsieh CL, Chen CH, Tseng YM, Shi GY, Wu HL, Tsai CH, Lin FY, Yeh HI. Therapeutic angiogenesis if human early endothelial progenitor cells is enhanced by thrombomodulin. Aterioscler Thromb Vasc Biol 2011;31:2518-2525.
Li WD, Hu N, Lei FR, Wei S, Rong JJ, Zhuang H, Li XQ. Autophagy inhibits endothelial progenitor cells migration via the regulation of MMP2, MMP9 and uPA under normoxia condition. Biochem Biophys Res Commun 2015;466:376-380.
MacFadyen J, Savage K, Wienke D, Isacke CM. Endosialin is expressed on stromal fibroblasts and CNS pericytes in mouse embryos and is downregulated during development. Gene Expr Patterns 2007;7:363-369.
MacFadyen JR, Haworth O, Roberston D, Hardie D, Webster MT, Morris HR, Panico M, Sutton-Smith M, Dell A, van der Geer P, Wienke D, Buckley CD, Isacke CM. Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium. FEBS Lett 2005;579:2569-2575.
Maia M, de Vriese A, Janssens T, Moons M, Lories RJ, Tavernier J, Conway EM. CD248 facilitates tumor growth via its cytoplasmic domain. BMC cancer 2011;11:162.
Maia M, de Vriese A, Janssens T, Moons M, van Landuyt K, Tavernier J, Lories RJ, Conway EM. CD248 and its cytoplasmic domain: a therapeutic target for arthritis. Arthritis Rheum 2010;62:3595-3606.
Martinet W, De Meyer GR. Autophagy in atherosclerosis: a cell survival and death phenomenon with therapeutic potential. Circ Res 2009;104:304-317.
Maruyama I, Bell CE, Majerus PW. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol 1985;101:363-371.
McLaughlin S, McNeill B, Podrebarac J, Hosoyama K, Sedlakova V, Cron G, Smyth D, Seymour R, Goel K, Liang W, Rayner KJ, Ruel M, Suuronen E, Alarcon E. Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction. Nat Commun 2019;10:4866.
Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451:1069-1075.
Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart 2007;93:1137-1146.
Murtha LA, Schullga MJ, Mabotuwana NS, Hardy SA, Waters DW, Burgess JK, Knight DA, Boyle AJ. The processes and mechanisms of cardiac and pulmonary fibrosis. Front Physiol 2017;8:777.
Nanda A, Karim B, Peng Z, Liu G, Qiu W, Gan C, Vogelstein B, St Croix B, Kinzier KW, Huso DL. Tumor endothelial marker 1 (Tem1) functions in the growth and progression of abdominal tumor. Proc Natl Acad Sci U S A 2006;103:3351-3356.
Opavsky R, Haviernik P, Jrkovicova D, Garin MT, Copeland NG, Gilbert DJ, Jenkins NA, Bies J, Garfield S, Pastorekova S, Oue A, Wolff L. Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo. J Biol Chem 2001;276:38795-38807.
Peng N, Meng N, Wang SQ, Zhao F, Zhao F, Su L, Zhang SL, Zhang Y, Zhao BX, Miao JY. An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E-/- mice. Sci Rep 2014;4:5519.
Pöschi E, Schlötzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y, Mayer U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 2004;131:1619-1628.
Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, Jimenez-Sanchez M, Korolchuk VI, Lichtenberg M, Luo S, Massey DC, Menzies FM, Moreau K, Narayanan U, Renna M, Siddiqi FH, Underwood R, Winslow AR, Rubinsztein D. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 2010;90:1383-1435.
Rettig WJ, Garin-Chesa P, Healey JH, Su SL, Jaffe EA, Old LJ. Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. Proc Natl Acad Sci USA 1992;89:10832-10836.
Rhoads JM, Niu X, Odle J, Graves LM. Role of mTOR signaling in intestinal cell migration. Am J Physiol Gastrointest Liver Physiol 2006;291:G510-G517.
Rmali KA, Puntis MC, Jiang WG. Prognostic values of tumor endothelial markers in patients with colorectal cancer. World J Gastroenterol 2005;11:1283-1286.
Roger VL, Weston SA, Redfield MM, Hellemann-Homan JP, Killian J, Yawn BP, Jacobsen SJ. Trends in heart failure incidence and survival in a community-based population. JAMA 2004;292:344-350.
Rupp C, Dolznig H, Puri C, Sommergruber W, Kerjaschki D, Rettig WJ, Garin-Chesa P. Mouse endosialin, a C-type lectin-like cell surface receptor: expression during embryonic development and induction in experimental cancer neoangiogenesis. Cancer Immun 2006;6:10-21.
Rybinski K, Imtiyaz HZ, Mittica B, Drozdowski B, Fulmer J, Furuuchi K, Fernando S, Henry M, Chao Q, Kline B, Albone E, Wustner J, Lin J, Nicolaides NC, Grasso L, Zhou Y. Targeting endosialin/CD248 through antibody-mediated internalization results in impaired pericyte maturation and dysfunctional tumor microvasculature. Oncotarget 2015;6:25429-25440.
Sala L, van Meer BJ, Tertoolen LGJ, Bakkers J, Bellin M, Davis RP, Denning C, Dieben MAE, Eschenhagen T, Giacomelli E, Grandela C, Hansen A, Holsen ER, Jongbloed MRM, Kamel SM, Koopman CD, Lachaud Q, Mannhardt I, Mol MPH, Mosqueira D, Orlova VV, Passier R, Ribeiro MC, Saleem U, Smith GL, Burton FL, Mummery CL. MUSCLEMOTION: A versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo. Circ Res 2018;122:e5-e16.
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012;9:676-682.
Shi CS, Shi GY, Chang YS, Han HS, Kuo CH, Liu C, Huang HC, Chang YJ, Chen PS, Wu HL. Evidence of human thrombomodulin domain as a novel angiogenic factor. Circulation 2005;111:1627-1636.
Skwarek-Maruszewska A, Hotulainen P, Mattila PK, Lappalainen P. Contractility-dependent actin dynamics in cardiomyocyte sarcomeres. J Cell Sci 2009;122:2119-2126.
Smith SW, Croft AP, Morris HL, Naylor AJ, Huso DL, Isacke CM, Savage CO, Buckley CD. Genetic deletion of the stromal cell marker CD248 (endosialin) protects against the development of renal fibrosis. Nephron 2015;131:265-277.
Smith SW, Eardley KS, Croft AP, Nwosu J, Howie AJ, Cockwell P, Isacke CM, Buckley CD, Savage CO. CD248+ stromal cells are associated with progressive chronic kidney disease. Kidney Int 2011;80:199-207.
Soff GA, Jackman RW, Rosenberg RD. Expression of thrombomodulin by smooth muscle cells in culture: different effects of tumor necrosis factor and cyclic adenosine monophosphate on thrombomodulin expression by endothelial cells and smooth muscle cells in culture. Blood 1991;77:515-518
St. Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW. Genes expressed in human tumor endothelium. Science 2000;289:1197-1202.
Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S. Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. EMBO J 1987;6:1891-1897.
Tarone G, Balligard JC, Bauersachs J, Clerk A, Windt LD, Heymans S, Hilfiker-Kleiner D, Hirsch E, Iaccarino G, Knöll R, Leite-Moreira AF, Lourenço AP, Mayr M, Thum T, Tocchetti CG. Targeting myocardial remodeling to develop novel therapies for heart failure: a position paper from the working group on myocardial function of European Society of Cardiology. Eur Heart J 2014;16:494-508.
Teicher BA. Newer vascular targets: endosialin (review). Int J Oncol 2007;30:305-312.
Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol 2015;89:1401-1438.
Tomkowicz B, Rybinski K, Foley B, Ebel W, Kline B, Routhier E, Sass P, Nicolaides NC, Grasso L, Zhou Y. Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration. Proc Natl Acad Sci U S A 2007;104:17965-17970.
Tomkowicz B, Rybinski K, Sebeck D, Sass P, Nicolaides NC, Grasso L, Zhou Y. Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling. Cancer Biol Ther 2010;9:908-915.
Torisu T, Torisu K, Lee IH, Liu J, Malide D, Combs CA, Wu XS, Rovira II, Fergusson MM, Weigert R, Connelly PS, Daniels MP, Komatsu M, Cao L, Finkel T. Autophagy regulates endothelial cell processing, maturation, and secretion of von Willebrand factor. Nat Med 2013;19:1281-1287.
Uchinaka A, Yoshida M, Tanaka K, Hamada Y, Mori S, Maeno Y, Miyagawa S, Sawa Y, Nagata K, Yamamoto H, Kawaguchi N. Overexpression of collagen type III in injured myocardium prevents cardiac systolic dysfunction by changing the balance of collagen distribution. J Thorac Cardiovasc Surg 2018;156:217-226.
Virgintino D, Girolamo F, Errede M, Capobianco C, Robertson D, Stallcup WB, Perris R, Roncali L. An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis. Angiogenesis 2007;10:35-45.
Wang HJ, Zhang D, Tan YZ, Li T. Autophagy in endothelial progenitor cells is cytoprotective in hypoxic conditions. Am J Physiol Cell Physiol 2013;304:C617-C626.
Watkins SJ, Borthwick GM, Arthur HM. The H9C2 cell line and primary neonatal cardiomyocyte cells show similar hypertrophic responses in vitro. In Vitro Cell Dev Biol Anim 2011;47:125-31.
Weber KT, Sun Y, Tyagi SC, Cleutjens JP. Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. J Mol Cell Cardiol 1994;26:279-292
Wei HJ, Li YH, Shi GY, Liu SL, Chang PC, Kuo CH, Wu HL. Thrombomodulin domains attenuate atherosclerosis by inhibiting thrombin-induced endothelial cell activation. Cardiovasc Res 2011;92:317-327.
Wen DZ, Dittman WA, Deaven LL, Majerus PW, Sadler JE. Human thrombomodulin: complete sDNA sequence and chromosome localization of the Gene. Biochemistry 1987;26:4350-4357.
Wilhelm A, Aldridge V, Haldar D, Naylor AJ, Weston CJ, Hedegaard D, Garg A, Fear J, Reynoids GM, Croft AP, Henderson NC, Buckley CD, Newsome PN. CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism. Gut 2016;65:1175-1185.
Xie M, Burchfield JS, Hill JA. Pathological ventricular remodeling: mechanisms: part 1 of 2. Ciculation 2013;128:388-400.
Zelensky AN, Gready JE. The C-type lectin-like domain superfamily. FEBS J 2005;272:6179-6217

校內：2023-01-01公開
校外：不公開電子論文尚未授權公開，紙本請查館藏目錄

簡易檢索 / 詳目顯示

相關論文