Ming-Zhi Zhang, M.D.

Assistant Professor

ming-zhi.zhang@vanderbilt.edu
Faculty Appointments
Assistant Professor of Medicine Assistant Professor of Cancer Biology
Education
M.Sc., Xuzhou Medical University, XuzhouM.D., Xuzhou Medical University, Xuzhou
Office Address
S-3206 MCN
TN 2175
Research Description
My research focuses on three main areas: <br>
1) Hormonal regulation of renal physiological and pathophysiologic functions. Specifically, we have investigated the regulation of renal cortical and medullary cyclooxygenase-2 (COX-2) expression by different hormones including elements of the renin-angiotensin system, dopaminergic system, adrenal corticosteroids, vasopressin, and others. We have also investigated the regulation of renal COX-2 by type II 11ß hydroxysteroid dehydrogenase (11ßHSD2) elevation of intracellular glucocorticoids. We are now intensively investigating the interaction between the intrarenal dopaminergic system and the intrarenal renin-angiotensin system using genetically manipulated mice with either elevated or reduced intrarenal dopaminergic activity. <br>
2) 11ßHSD2 and colorectal tumorigenesis. COX-2 expression increases in colorectal tumors. Inhibition of COX-2 activity suppresses colorectal tumorigenesis. Both COX-2 and 11ßHSD2 expression are elevated in colorectal adenomas. Glucocorticoids are potent endogenous 11ßHSD2 inhibitors. Inhibition of 11ßHSD2 activity elevates levels of intracellular glucocorticoids in tumor cells, leading to inhibition of both COX-2 and tumorigenesis.<br>
3) Immunohistochemistry in the kidney, application of image analysis and tissue microarray (TMA) in kidney research.
Research Keywords
kidney, diabetes, dopamine, colorectal cancer, 11betaHSD2, COX-2, LOX
Publications
Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, Yin H, Yang S, Harris RC. Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. J. Clin. Invest [print-electronic]. 2011 Jul; 121(7): 2845-54. PMID: 21701066, PMCID: PMC3223841, PII: 57324, DOI: 10.1172/JCI57324, ISSN: 1558-8238.

Chen X, Whiting C, Borza C, Hu W, Mont S, Bulus N, Zhang MZ, Harris RC, Zent R, Pozzi A. Integrin alpha1beta1 regulates epidermal growth factor receptor activation by controlling peroxisome proliferator-activated receptor gamma-dependent caveolin-1 expression. Mol. Cell. Biol [print-electronic]. 2010 Jun; 30(12): 3048-58. PMID: 20368353, PMCID: PMC2876688, PII: MCB.00892-09, DOI: 10.1128/MCB.00892-09, ISSN: 1098-5549.

Zhang MZ, Su Y, Yao B, Zheng W, Decaestecker M, Harris RC. Assessing the application of tissue microarray technology to kidney research. J. Histochem. Cytochem [print-electronic]. 2010 May; 58(5): 413-20. PMID: 20086233, PMCID: PMC2857813, PII: jhc.2009.954966, DOI: 10.1369/jhc.2009.954966, ISSN: 1551-5044.

He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, Yang HC, Fogo AB, Zent R, Harris RC, Breyer MD, Hao CM. Sirt1 activation protects the mouse renal medulla from oxidative injury. J. Clin. Invest [print-electronic]. 2010 Apr; 120(4): 1056-68. PMID: 20335659, PMCID: PMC2846063, PII: 41563, DOI: 10.1172/JCI41563, ISSN: 1558-8238.

Yao B, Harris RC, Zhang MZ. Intrarenal dopamine attenuates deoxycorticosterone acetate/high salt-induced blood pressure elevation in part through activation of a medullary cyclooxygenase 2 pathway. Hypertension [print-electronic]. 2009 Nov; 54(5): 1077-83. PMID: 19770404, PMCID: PMC2782522, PII: HYPERTENSIONAHA.109.137174, DOI: 10.1161/HYPERTENSIONAHA.109.137174, ISSN: 1524-4563.

Zhang MZ, Xu J, Yao B, Yin H, Cai Q, Shrubsole MJ, Chen X, Kon V, Zheng W, Pozzi A, Harris RC. Inhibition of 11beta-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. J. Clin. Invest [print-electronic]. 2009 Apr; 119(4): 876-85. PMID: 19307727, PMCID: PMC2662561, PII: 37398, DOI: 10.1172/JCI37398, ISSN: 1558-8238.

Zhang MZ, Yao B, Fang X, Wang S, Smith JP, Harris RC. Intrarenal dopaminergic system regulates renin expression. Hypertension [print-electronic]. 2009 Mar; 53(3): 564-70. PMID: 19139376, PMCID: PMC2680004, PII: HYPERTENSIONAHA.108.127035, DOI: 10.1161/HYPERTENSIONAHA.108.127035, ISSN: 1524-4563.

Yao B, Xu J, Harris RC, Zhang MZ. Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase. Am. J. Physiol. Renal Physiol [print-electronic]. 2008 Feb; 294(2): F433-9. PMID: 18057186, PII: 00436.2007, DOI: 10.1152/ajprenal.00436.2007, ISSN: 1931-857X.

Zeng F, Zhang MZ, Singh AB, Zent R, Harris RC. ErbB4 isoforms selectively regulate growth factor induced Madin-Darby canine kidney cell tubulogenesis. Mol. Biol. Cell [print-electronic]. 2007 Nov; 18(11): 4446-56. PMID: 17761534, PMCID: PMC2043549, PII: E07-03-0223, DOI: 10.1091/mbc.E07-03-0223, ISSN: 1059-1524.

Xu J, Yao B, Fan X, Langworthy MM, Zhang MZ, Harris RC. Characterization of a putative intrarenal serotonergic system. Am. J. Physiol. Renal Physiol [print-electronic]. 2007 Nov; 293(5): F1468-75. PMID: 17715266, PII: 00246.2007, DOI: 10.1152/ajprenal.00246.2007, ISSN: 1931-857X.

Cheng H, Wang S, Jo YI, Hao CM, Zhang M, Fan X, Kennedy C, Breyer MD, Moeckel GW, Harris RC. Overexpression of cyclooxygenase-2 predisposes to podocyte injury. J. Am. Soc. Nephrol [print-electronic]. 2007 Feb; 18(2): 551-9. PMID: 17202413, PII: ASN.2006090990, DOI: 10.1681/ASN.2006090990, ISSN: 1046-6673.

Zhang MZ, Yao B, Cheng HF, Wang SW, Inagami T, Harris RC. Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT(1) and AT(2) receptors. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2006 Oct 10/24/2006; 103(43): 16045-50. PMID: 17043228, PMCID: PMC1635124, PII: 0602176103, DOI: 10.1073/pnas.0602176103, ISSN: 0027-8424.

Zhao HJ, Wang S, Cheng H, Zhang MZ, Takahashi T, Fogo AB, Breyer MD, Harris RC. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. J. Am. Soc. Nephrol [print-electronic]. 2006 Oct; 17(10): 2664-9. PMID: 16971655, PMCID: PMC4618687, PII: ASN.2006070798, DOI: 10.1681/ASN.2006070798, ISSN: 1046-6673.

Yao B, Xu J, Qi Z, Harris RC, Zhang MZ. Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake. Am. J. Physiol. Renal Physiol [print-electronic]. 2006 Aug; 291(2): F368-74. PMID: 16597606, PII: 00500.2005, DOI: 10.1152/ajprenal.00500.2005, ISSN: 1931-857X.

Cheng HF, Zhang MZ, Harris RC. Nitric oxide stimulates cyclooxygenase-2 in cultured cTAL cells through a p38-dependent pathway. Am. J. Physiol. Renal Physiol [print-electronic]. 2006 Jun; 290(6): F1391-7. PMID: 16380459, PII: 00315.2005, DOI: 10.1152/ajprenal.00315.2005, ISSN: 1931-857X.

Yao B, Harris RC, Zhang MZ. Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2005 Jun; 288(6): R1767-73. PMID: 15718388, PII: 00786.2004, DOI: 10.1152/ajpregu.00786.2004, ISSN: 0363-6119.

Zhang MZ, Yao B, McKanna JA, Harris RC. Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems. Am. J. Physiol. Renal Physiol [print-electronic]. 2005 Apr; 288(4): F840-5. PMID: 15613619, PII: 00240.2004, DOI: 10.1152/ajprenal.00240.2004, ISSN: 1931-857X.

Rao R, Zhang MZ, Zhao M, Cai H, Harris RC, Breyer MD, Hao CM. Lithium treatment inhibits renal GSK-3 activity and promotes cyclooxygenase 2-dependent polyuria. Am. J. Physiol. Renal Physiol [print-electronic]. 2005 Apr; 288(4): F642-9. PMID: 15585669, PII: 00287.2004, DOI: 10.1152/ajprenal.00287.2004, ISSN: 1931-857X.

Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC. Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition. Nephron Exp. Nephrol [print-electronic]. 2005; 101(3): e75-85. PMID: 15995341, PII: 86645, DOI: 10.1159/000086645, ISSN: 1660-2129.

Harris RC, Zhang MZ, Cheng HF. Cyclooxygenase-2 and the renal renin-angiotensin system. Acta Physiol. Scand. 2004 Aug; 181(4): 543-7. PMID: 15283769, PII: APS1329, DOI: 10.1111/j.1365-201X.2004.01329.x, ISSN: 0001-6772.

Schneider A, Zhang Y, Zhang M, Lu WJ, Rao R, Fan X, Redha R, Davis L, Breyer RM, Harris R, Guan Y, Breyer MD. Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney. Kidney Int. 2004 Apr; 65(4): 1205-13. PMID: 15086459, DOI: 10.1111/j.1523-1755.2004.00493.x, ISSN: 0085-2538.

Zhang MZ, Sanchez Lopez P, McKanna JA, Harris RC. Regulation of cyclooxygenase expression by vasopressin in rat renal medulla. Endocrinology [print-electronic]. 2004 Mar; 145(3): 1402-9. PMID: 14684611, PII: en.2003-0903, DOI: 10.1210/en.2003-0903, ISSN: 0013-7227.

Zhang MZ, Mai W, Li C, Cho SY, Hao C, Moeckel G, Zhao R, Kim I, Wang J, Xiong H, Wang H, Sato Y, Wu Y, Nakanuma Y, Lilova M, Pei Y, Harris RC, Li S, Coffey RJ, Sun L, Wu D, Chen XZ, Breyer MD, Zhao ZJ, McKanna JA, Wu G. PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 2004 Feb 2/24/2004; 101(8): 2311-6. PMID: 14983006, PMCID: PMC356947, PII: 101/8/2311, ISSN: 0027-8424.

Zhang MZ, Wang SW, Cheng H, Zhang Y, McKanna JA, Harris RC. Regulation of renal cortical cyclooxygenase-2 in young rats. Am. J. Physiol. Renal Physiol [print-electronic]. 2003 Nov; 285(5): F881-8. PMID: 12851252, PII: 00154.2003, DOI: 10.1152/ajprenal.00154.2003, ISSN: 1931-857X.

Cheng HF, Wang SW, Zhang MZ, McKanna JA, Breyer R, Harris RC. Prostaglandins that increase renin production in response to ACE inhibition are not derived from cyclooxygenase-1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002 Sep; 283(3): R638-46. PMID: 12184998, DOI: 10.1152/ajpregu.00150.2002, ISSN: 0363-6119.

Zhang MZ, Hao CM, Breyer MD, Harris RC, McKanna JA. Mineralocorticoid regulation of cyclooxygenase-2 expression in rat renal medulla. Am. J. Physiol. Renal Physiol. 2002 Sep; 283(3): F509-16. PMID: 12167602, DOI: 10.1152/ajprenal.00236.2001, ISSN: 1931-857X.

Cheng HF, Wang CJ, Moeckel GW, Zhang MZ, McKanna JA, Harris RC. Cyclooxygenase-2 inhibitor blocks expression of mediators of renal injury in a model of diabetes and hypertension. Kidney Int. 2002 Sep; 62(3): 929-39. PMID: 12164875, PII: kid520, DOI: 10.1046/j.1523-1755.2002.00520.x, ISSN: 0085-2538.

Cheng HF, Wang JL, Zhang MZ, Wang SW, McKanna JA, Harris RC. Genetic deletion of COX-2 prevents increased renin expression in response to ACE inhibition. Am. J. Physiol. Renal Physiol. 2001 Mar; 280(3): F449-56. PMID: 11181406, ISSN: 1931-857X.

Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC. Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride. J. Clin. Invest. 2000 Sep; 106(5): 681-8. PMID: 10974021, PMCID: PMC381289, DOI: 10.1172/JCI10318, ISSN: 0021-9738.

Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC. Nitric oxide regulates renal cortical cyclooxygenase-2 expression. Am. J. Physiol. Renal Physiol. 2000 Jul; 279(1): F122-9. PMID: 10894794, ISSN: 1931-857X.

Harris RC, Cheng H, Wang J, Zhang M, McKanna JA. Interactions of the renin-angiotensin system and neuronal nitric oxide synthase in regulation of cyclooxygenase-2 in the macula densa. Acta Physiol. Scand. 2000 Jan; 168(1): 47-51. PMID: 10691779, PII: aps642, DOI: 10.1046/j.1365-201x.2000.00642.x, ISSN: 0001-6772.

Zhang MZ, Harris RC, McKanna JA. Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids. Proc. Natl. Acad. Sci. U.S.A. 1999 Dec 12/21/1999; 96(26): 15280-5. PMID: 10611376, PMCID: PMC24811, ISSN: 0027-8424.

Cheng HF, Wang JL, Zhang MZ, Miyazaki Y, Ichikawa I, McKanna JA, Harris RC. Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. J. Clin. Invest. 1999 Apr; 103(7): 953-61. PMID: 10194467, PMCID: PMC408259, DOI: 10.1172/JCI5505, ISSN: 0021-9738.

Zhang MC, He L, Giro M, Yong SL, Tiller GE, Davidson JM. Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN). J. Biol. Chem. 1999 Jan 1/8/1999; 274(2): 981-6. PMID: 9873040, ISSN: 0021-9258.

Wang JL, Cheng HF, Zhang MZ, McKanna JA, Harris RC. Selective increase of cyclooxygenase-2 expression in a model of renal ablation. Am. J. Physiol. 1998 Oct; 275(4 Pt 2): F613-22. PMID: 9755133, ISSN: 0002-9513.

Harris RC, Wang JL, Cheng HF, Zhang MZ, McKanna JA. Prostaglandins in macula densa function. Kidney Int. Suppl. 1998 Sep; 67: S49-52. PMID: 9736253, ISSN: 0098-6577.

McKanna JA, Zhang MZ, Wang JL, Cheng H, Harris RC. Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am. J. Physiol. 1998 Jul; 275(1 Pt 2): R227-33. PMID: 9688983, ISSN: 0002-9513.

Zhang MZ, Wang JL, Cheng HF, Harris RC, McKanna JA. Cyclooxygenase-2 in rat nephron development. Am. J. Physiol. 1997 Dec; 273(6 Pt 2): F994-1002. PMID: 9435689, ISSN: 0002-9513.

Melzer P, Zhang MZ, McKanna JA. Infraorbital nerve transection and whisker follicle removal in adult rats affect microglia and astrocytes in the trigeminal brainstem. A study with lipocortin1- and S100beta-immunohistochemistry. Neuroscience. 1997 Sep; 80(2): 459-72. PMID: 9284349, PII: S0306452296006938, ISSN: 0306-4522.

Zhang MZ, McKanna JA. Gliogenesis in postnatal rat optic nerve: LC1 + microglia and S100-beta + astrocytes. Brain Res. Dev. Brain Res. 1997 Jul 7/18/1997; 101(1-2): 27-36. PMID: 9263577, ISSN: 0165-3806.

Sakai M, Zhang M, Homma T, Garrick B, Abraham JA, McKanna JA, Harris RC. Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules. J. Clin. Invest. 1997 May 5/1/1997; 99(9): 2128-38. PMID: 9151785, PMCID: PMC508043, DOI: 10.1172/JCI119386, ISSN: 0021-9738.

McKanna JA, Zhang MZ. Immunohistochemical localization of lipocortin 1 in rat brain is sensitive to pH, freezing, and dehydration. J. Histochem. Cytochem. 1997 Apr; 45(4): 527-38. PMID: 9111231, ISSN: 0022-1554.