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Satoru Eguchi, MD, PhD

Professor, Physiology

Professor, Cardiovascular Research Center

Professor, Sol Sherry Thrombosis Research Center

Telephone:  215-707-0169

Fax:  215-707-5737

Office: MERB 1051

Email: seguchi@temple.edu

Department of Physiology

Cardiovascular Research Center

Sol Sherry Thrombosis Research Center

MD, 1987

Tohoku University School of Medicine

Sendai, Japan

 

PhD, 1993

Tokyo Medical and Dental University

Tokyo, Japan

 

Postdoctoral Fellowship, 1994

Vanderbilt University School of Medicine

Nashville, TN

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My lab is currently studying the mechanism of signal transduction of vascular smooth muscle cells (VSMCs) and endothelial cells leading to VSMC remodeling and endothelial dysfunction, respectively.  These two major abnormalities are believed to be the critical points leading to irreversible cardiovascular diseases. 

The subjects include:

1) Signaling of a potent cardiovascular pathogen angiotensin II (AngII) in mediating migration and growth of VSMCs. 

1-A.  EGF receptor transactivation by AngII: My lab is leading this area by several key publications demonstrating the involvement of Gq protein, a metalloprotease (ADAM), HB-EGF, and reactive oxygen species in the EGF receptor transactivation resulting in ERK activation, migration and hypertrophy of VSMCs.  We are currently focusing on identification of ADAM together with its mechanism of activation (Figure). The approaches include cell lines from ADAM deleted mice, dominant-negative mutant expression in VSMC by adenovirus and retrovirus, shedding assay by using HB-EGF/ALP chimera construct, deletion and mutation of ADAM constructs tagged with GFP and GST to analyze protein-protein interaction, phosphorylation, and subcellular localization, and ADAM activity assay by using a fluogenic substrate.  Since EGFR transactivation has been shown in cancer and inflammation, the significances of expected findings are not solely limited in vascular biology and pathophysiology.

1-B. Rho/Rho kinase regulation by AngII.

Although importance of Rho kinase in mediating Ca2+ sensitization in VSMCs is well established, the detailed mechanism by which vasoconstrictors such as AngII mediating Rho kinase activation and whether Rho kinase mediates other pathogenic function of Ang II remain unclear.  We recently found that AngII signals to Rho kinase via PKCdelta and PYK2 leading to JNK-dependent VSMC migration. The research could provide novel mechanisms of vascular diseases induced by vasoconstrictors and our expected findings could be expanded to understand the regulation of small G protein by GPCRs.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

23535568. Takayanagi T, Eguchi A, Takaguri A, Hinoki A, Bourne AM, Elliott KJ, Hurlin PJ, Eguchi S, A repressor protein, Mnt, is a novel negative regulator of vascular smooth muscle cell hypertrophy by angiotensin II and neointimal hyperplasia by arterial injury. Atherosclerosis 228:1(90-3)2013 May

22113169. Takayanagi T, Bourne AM, Kimura K, Takaguri A, Elliott KJ, Eguchi K, Eguchi S, Constitutive stimulation of vascular smooth muscle cells by angiotensin II derived from an adenovirus encoding a furin-cleavable fusion protein. Am J Hypertens 25:3(280-3)2012 Mar

21927009. Bourne AM, Eguchi S, Angiotensin II causes vascular smooth muscle insulin resistance: attractive mechanism but more to clarify. Am J Hypertens 24:10(1057-8)2011 Oct

21357274. Takaguri A, Kimura K, Hinoki A, Bourne AM, Autieri MV, Eguchi S, A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature. Hypertension 57:4(841-5)2011 Apr

21172357. Takaguri A, Shirai H, Kimura K, Hinoki A, Eguchi K, Carlile-Klusacek M, Yang B, Rizzo V, Eguchi S, Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II. J Mol Cell Cardiol 50:3(545-51)2011 Mar

21071702. Smolock AR, Mishra G, Eguchi K, Eguchi S, Scalia R, Protein kinase C upregulates intercellular adhesion molecule-1 and leukocyte-endothelium interactions in hyperglycemia via activation of endothelial expressed calpain. Arterioscler Thromb Vasc Biol 31:2(289-96)2011 Feb

20929813. Wang Y, Deng X, Mancarella S, Hendron E, Eguchi S, Soboloff J, Tang XD, Gill DL, The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels. Science 330:6000(105-9)2010 Oct 1

19901155. Hinoki A, Kimura K, Higuchi S, Eguchi K, Takaguri A, Ishimaru K, Frank GD, Gerthoffer WT, Sommerville LJ, Autieri MV, Eguchi S, p21-activated kinase 1 participates in vascular remodeling in vitro and in vivo. Hypertension 55:1(161-5)2010 Jan

19095998. Suzuki H, Kimura K, Shirai H, Eguchi K, Higuchi S, Hinoki A, Ishimaru K, Brailoiu E, Dhanasekaran DN, Stemmle LN, Fields TA, Frank GD, Autieri MV, Eguchi S, Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration. Arterioscler Thromb Vasc Biol 29:2(217-24)2009 Feb

19064814. Suzuki H, Motley ED, Eguchi K, Hinoki A, Shirai H, Watts V, Stemmle LN, Fields TA, Eguchi S, Distinct roles of protease-activated receptors in signal transduction regulation of endothelial nitric oxide synthase. Hypertension 53:2(182-8)2009 Feb

18779232. Sommerville LJ, Xing C, Kelemen SE, Eguchi S, Autieri MV, Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity. Cardiovasc Res 81:1(206-15)2009 Jan 1

18356277. Ohtsu H, Higuchi S, Shirai H, Eguchi K, Suzuki H, Hinoki A, Brailoiu E, Eckhart AD, Frank GD, Eguchi S, Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells. Endocrinology 149:7(3569-75)2008 Jul

18180404. Nakashima H, Frank GD, Shirai H, Hinoki A, Higuchi S, Ohtsu H, Eguchi K, Sanjay A, Reyland ME, Dempsey PJ, Inagami T, Eguchi S, Novel role of protein kinase C-delta Tyr 311 phosphorylation in vascular smooth muscle cell hypertrophy by angiotensin II. Hypertension 51:2(232-8)2008 Feb

17346243. Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S, Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. Clin Sci (Lond) 112:8(417-28)2007 Apr

17293685. Shirai H, Autieri M, Eguchi S, Small GTP-binding proteins and mitogen-activated protein kinases as promising therapeutic targets of vascular remodeling. Curr Opin Nephrol Hypertens 16:2(111-5)2007 Mar

17080158. Suzuki H, Eguchi S, Adiponectin versus angiotensin II: Key pathological role of their misbalance. Kidney Int 70:10(1678-9)2006 Nov

16980435. Suzuki H, Eguchi K, Ohtsu H, Higuchi S, Dhobale S, Frank GD, Motley ED, Eguchi S, Activation of endothelial nitric oxide synthase by the angiotensin II type 1 receptor. Endocrinology 147:12(5914-20)2006 Dec

16923993. Ohtsu H, Suzuki H, Nakashima H, Dhobale S, Frank GD, Motley ED, Eguchi S, Angiotensin II signal transduction through small GTP-binding proteins: mechanism and significance in vascular smooth muscle cells. Hypertension 48:4(534-40)2006 Oct

16840716. Ohtsu H, Dempsey PJ, Frank GD, Brailoiu E, Higuchi S, Suzuki H, Nakashima H, Eguchi K, Eguchi S, ADAM17 mediates epidermal growth factor receptor transactivation and vascular smooth muscle cell hypertrophy induced by angiotensin II. Arterioscler Thromb Vasc Biol 26:9(e133-7)2006 Sep

16769815. Ohtsu H, Dempsey PJ, Eguchi S, ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am J Physiol Cell Physiol 291:1(C1-10)2006 Jul

16724941. Suzuki H, Frank GD, Utsunomiya H, Higuchi S, Eguchi S, Current understanding of the mechanism and role of ROS in angiotensin II signal transduction. Curr Pharm Biotechnol 7:2(81-6)2006 Apr

16472178. Nakashima H, Suzuki H, Ohtsu H, Chao JY, Utsunomiya H, Frank GD, Eguchi S, Angiotensin II regulates vascular and endothelial dysfunction: recent topics of Angiotensin II type-1 receptor signaling in the vasculature. Curr Vasc Pharmacol 4:1(67-78)2006 Jan

16250862. Suzuki H, Motley ED, Frank GD, Utsunomiya H, Eguchi S, Recent progress in signal transduction research of the angiotensin II type-1 receptor: protein kinases, vascular dysfunction and structural requirement. Curr Med Chem Cardiovasc Hematol Agents 3:4(305-22)2005 Oct

16115037. Ohtsu H, Frank GD, Utsunomiya H, Eguchi S, Redox-dependent protein kinase regulation by angiotensin II: mechanistic insights and its pathophysiology. Antioxid Redox Signal 7:9-10(1315-26)2005 Sep-Oct

15998260. Frank GD, Eguchi S, Motley ED, The role of reactive oxygen species in insulin signaling in the vasculature. Antioxid Redox Signal 7:7-8(1053-61)2005 Jul-Aug

15994438. Ohtsu H, Mifune M, Frank GD, Saito S, Inagami T, Kim-Mitsuyama S, Takuwa Y, Sasaki T, Rothstein JD, Suzuki H, Nakashima H, Woolfolk EA, Motley ED, Eguchi S, Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin II. Arterioscler Thromb Vasc Biol 25:9(1831-6)2005 Sep

15905175. Mifune M, Ohtsu H, Suzuki H, Nakashima H, Brailoiu E, Dun NJ, Frank GD, Inagami T, Higashiyama S, Thomas WG, Eckhart AD, Dempsey PJ, Eguchi S, G protein coupling and second messenger generation are indispensable for metalloprotease-dependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor. J Biol Chem 280:28(26592-9)2005 Jul 15

15163624. Mifune M, Ohtsu H, Suzuki H, Frank GD, Inagami T, Utsunomiya H, Dempsey PJ, Eguchi S, Signal transduction of betacellulin in growth and migration of vascular smooth muscle cells. Am J Physiol Cell Physiol 287:3(C807-13)2004 Sep

14641025. Eguchi S, Frank GD, Mifune M, Inagami T, Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling. Biochem Soc Trans 31:Pt 6(1198-202)2003 Dec

14588150. Frank GD, Eguchi S, Activation of tyrosine kinases by reactive oxygen species in vascular smooth muscle cells: significance and involvement of EGF receptor transactivation by angiotensin II. Antioxid Redox Signal 5:6(771-80)2003 Dec

12588978. Frank GD, Mifune M, Inagami T, Ohba M, Sasaki T, Higashiyama S, Dempsey PJ, Eguchi S, Distinct mechanisms of receptor and nonreceptor tyrosine kinase activation by reactive oxygen species in vascular smooth muscle cells: role of metalloprotease and protein kinase C-delta. Mol Cell Biol 23:5(1581-9)2003 Mar

12226102. Saito S, Frank GD, Mifune M, Ohba M, Utsunomiya H, Motley ED, Inagami T, Eguchi S, Ligand-independent trans-activation of the platelet-derived growth factor receptor by reactive oxygen species requires protein kinase C-delta and c-Src. J Biol Chem 277:47(44695-700)2002 Nov 22

12074579. Saito S, Frank GD, Motley ED, Dempsey PJ, Utsunomiya H, Inagami T, Eguchi S, Metalloprotease inhibitor blocks angiotensin II-induced migration through inhibition of epidermal growth factor receptor transactivation. Biochem Biophys Res Commun 294:5(1023-9)2002 Jun 28

12044791. Saito S, Frank GD, Motley ED, Utsunomiya H, Inagami T, Eguchi S, Cyclosporin A inhibits angiotensin II-induced c-Jun NH(2)-terminal kinase activation but not protein synthesis in vascular smooth muscle cells. Eur J Pharmacol 443:1-3(47-50)2002 May 17

11818507. Frank GD, Saito S, Motley ED, Sasaki T, Ohba M, Kuroki T, Inagami T, Eguchi S, Requirement of Ca(2+) and PKCdelta for Janus kinase 2 activation by angiotensin II: involvement of PYK2. Mol Endocrinol 16:2(367-77)2002 Feb

11520052. Frank GD, Eguchi S, Motley ED, Sasaki T, Inagami T, Unique regulation of c-Jun N-terminal kinase by PYK2/CAK-beta in angiotensin II-stimulated vascular smooth muscle cells. Biochem Biophys Res Commun 286:4(692-6)2001 Aug 31

11116149. Eguchi S, Dempsey PJ, Frank GD, Motley ED, Inagami T, Activation of MAPKs by angiotensin II in vascular smooth muscle cells. Metalloprotease-dependent EGF receptor activation is required for activation of ERK and p38 MAPK but not for JNK. J Biol Chem 276:11(7957-62)2001 Mar 16

10967198. Eguchi S, Inagami T, Signal transduction of angiotensin II type 1 receptor through receptor tyrosine kinase. Regul Pept 91:1-3(13-20)2000 Jul 28

10829089. Inagami T, Eguchi S, Angiotensin II-mediated vascular smooth muscle cell growth signaling. Braz J Med Biol Res 33:6(619-24)2000 Jun

10772898. Frank GD, Motley ED, Inagami T, Eguchi S, PYK2/CAKbeta represents a redox-sensitive tyrosine kinase in vascular smooth muscle cells. Biochem Biophys Res Commun 270:3(761-5)2000 Apr 21

10601235. Eguchi S, Iwasaki H, Ueno H, Frank GD, Motley ED, Eguchi K, Marumo F, Hirata Y, Inagami T, Intracellular signaling of angiotensin II-induced p70 S6 kinase phosphorylation at Ser(411) in vascular smooth muscle cells. Possible requirement of epidermal growth factor receptor, Ras, extracellular signal-regulated kinase, and Akt. J Biol Chem 274:52(36843-51)1999 Dec 24

10440105. Eguchi S, Iwasaki H, Hirata Y, Frank GD, Motley ED, Yamakawa T, Numaguchi K, Inagami T, Epidermal growth factor receptor is indispensable for c-Fos expression and protein synthesis by angiotensin II. Eur J Pharmacol 376:1-2(203-6)1999 Jul 2

10433212. Yamakawa T, Eguchi S, Matsumoto T, Yamakawa Y, Numaguchi K, Miyata I, Reynolds CM, Motley ED, Inagami T, Intracellular signaling in rat cultured vascular smooth muscle cells: roles of nuclear factor-kappaB and p38 mitogen-activated protein kinase on tumor necrosis factor-alpha production. Endocrinology 140:8(3562-72)1999 Aug

10405785. Inagami T, Kambayashi Y, Ichiki T, Tsuzuki S, Eguchi S, Yamakawa T, Angiotensin receptors: molecular biology and signalling. Clin Exp Pharmacol Physiol 26:7(544-9)1999 Jul

10400905. Numaguchi K, Eguchi S, Yamakawa T, Motley ED, Inagami T, Mechanotransduction of rat aortic vascular smooth muscle cells requires RhoA and intact actin filaments. Circ Res 85:1(5-11)1999 Jul 9

9892141. Inagami T, Eguchi S, Numaguchi K, Motley ED, Tang H, Matsumoto T, Yamakawa T, Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases. J Am Soc Nephrol 10 Suppl 11:(S57-61)1999 Jan

9535870. Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomiya H, Motley ED, Kawakatsu H, Owada KM, Hirata Y, Marumo F, Inagami T, Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 273:15(8890-6)1998 Apr 10

9453311. Yamakawa T, Eguchi S, Yamakawa Y, Motley ED, Numaguchi K, Utsunomiya H, Inagami T, Lysophosphatidylcholine stimulates MAP kinase activity in rat vascular smooth muscle cells. Hypertension 31:1 Pt 2(248-53)1998 Jan

9387061. Inagami T, Eguchi S, Tsuzuki S, Ichiki T, Angiotensin II receptors AT1 and AT2--new mechanisms of signaling and antagonistic effects of AT1 and AT2. Jpn Circ J 61:10(807-13)1997 Oct

8941361. Tsuzuki S, Eguchi S, Inagami T, Inhibition of cell proliferation and activation of protein tyrosine phosphatase mediated by angiotensin II type 2 (AT2) receptor in R3T3 cells. Biochem Biophys Res Commun 228:3(825-30)1996 Nov 21

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Postdoctoral Fellows

Akira Takaguri          takira@temple.edu                   T: 215-707-8378

 

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Kunie Eguchi

Senior Laboratory Technician

T:  215-707-8378

F:  215-707-5737

Email address: kunie.eguchi@temple.edu

Kathy Elliott

Research Associate II

Email address: kelliott@temple.edu

Katsuhiro Okuda

Assistant Scientist

Email address: katsuhiro.okuda@temple.edu

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