Contact Information
Vanderbilt Center for Kidney Disease Vanderbilt Division of Nephrology S-3223 Medical Center North Nashville, TN 37232-2372 615 322-2150 (phone) 615 343-2675 (fax)
Ming-Zhi Zhang M.D.
Department: Medicine
Biography
My research focuses on three main areas:
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.
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.
3) Immunohistochemistry in the kidney, application of image analysis and tissue microarray (TMA) in kidney research.
Featured Publications
1. Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.
Ding ZY, Liang HF, Jin GN, Chen WX, Wang W, Datta PK, Zhang MZ, Zhang B, Chen XP (2014) J Cell Physiol 229(5): 651-60
Citation ⋅ 24446200 (PubMed)2. Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney.
Zhang MZ, Wang Y, Yao B, Gewin L, Wei S, Capdevila JH, Harris RC (2013) Am J Physiol Renal Physiol 305(12): F1680-6
Citation ⋅ 24154693 (PubMed) PMC3882452 (PubMed Central)3. 11β-Hydroxysteroid Dehydrogenase Type II is a Potential Target for Prevention of Colorectal Tumorigenesis.
Yang S, Jiang L, Zhang MZ (2013) J Oncobiomarkers 1(1):
Citation ⋅ 23936870 (PubMed) PMC3736594 (PubMed Central)Publications
1. Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.
Ding ZY, Liang HF, Jin GN, Chen WX, Wang W, Datta PK, Zhang MZ, Zhang B, Chen XP (2014) J Cell Physiol 229(5): 651-60
Citation ⋅ 24446200 (PubMed)2. Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney.
Zhang MZ, Wang Y, Yao B, Gewin L, Wei S, Capdevila JH, Harris RC (2013) Am J Physiol Renal Physiol 305(12): F1680-6
Citation ⋅ 24154693 (PubMed) PMC3882452 (PubMed Central)3. 11β-Hydroxysteroid Dehydrogenase Type II is a Potential Target for Prevention of Colorectal Tumorigenesis.
Yang S, Jiang L, Zhang MZ (2013) J Oncobiomarkers 1(1):
Citation ⋅ 23936870 (PubMed) PMC3736594 (PubMed Central)4. Epithelial-specific deletion of 11β-HSD2 hinders Apcmin/+ mouse tumorigenesis.
Jiang L, Yang S, Yin H, Fan X, Wang S, Yao B, Pozzi A, Chen X, Harris RC, Zhang MZ (2013) Mol Cancer Res 11(9): 1040-50
Citation ⋅ 23741059 (PubMed) PMC3778073 (PubMed Central)5. Cyclooxygenase metabolites in the kidney.
Harris RC, Zhang MZ (2011) Compr Physiol 1(4): 1729-58
Citation ⋅ 23733687 (PubMed)6. Transforming growth factor β induces expression of connective tissue growth factor in hepatic progenitor cells through Smad independent signaling.
Ding ZY, Jin GN, Liang HF, Wang W, Chen WX, Datta PK, Zhang MZ, Zhang B, Chen XP (2013) Cell Signal 25(10): 1981-92
Citation ⋅ 23727026 (PubMed)7. CSF-1 signaling mediates recovery from acute kidney injury.
Zhang MZ, Yao B, Yang S, Jiang L, Wang S, Fan X, Yin H, Wong K, Miyazawa T, Chen J, Chang I, Singh A, Harris RC (2012) J Clin Invest 122(12): 4519-32
Citation ⋅ 23143303 (PubMed) PMC3533529 (PubMed Central)8. Association of high blood pressure with renal insufficiency: role of albuminuria, from NHANES, 1999-2006.
Yan P, Zhu X, Li H, Shrubsole MJ, Shi H, Zhang MZ, Harris RC, Hao CM, Dai Q (2012) PLoS One 7(7): e37837
Citation ⋅ 22802927 (PubMed) PMC3388992 (PubMed Central)9. Intrarenal dopamine inhibits progression of diabetic nephropathy.
Zhang MZ, Yao B, Yang S, Yang H, Wang S, Fan X, Yin H, Fogo AB, Moeckel GW, Harris RC (2012) Diabetes 61(10): 2575-84
Citation ⋅ 22688335 (PubMed) PMC3447896 (PubMed Central)10. Dopamine, the kidney, and hypertension.
Harris RC, Zhang MZ (2012) Curr Hypertens Rep 14(2): 138-43
Citation ⋅ 22407378 (PubMed) PMC3742329 (PubMed Central)11. New isoform-specific monoclonal antibodies reveal different sub-cellular localisations for talin1 and talin2.
Praekelt U, Kopp PM, Rehm K, Linder S, Bate N, Patel B, Debrand E, Manso AM, Ross RS, Conti F, Zhang MZ, Harris RC, Zent R, Critchley DR, Monkley SJ (2012) Eur J Cell Biol 91(3): 180-91
Citation ⋅ 22306379 (PubMed) PMC3629562 (PubMed Central)12. Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury.
Yang S, Yao B, Zhou Y, Yin H, Zhang MZ, Harris RC (2012) Am J Physiol Renal Physiol 302(6): F742-9
Citation ⋅ 22169008 (PubMed) PMC3311314 (PubMed Central)13. Role of blood pressure and the renin-angiotensin system in development of diabetic nephropathy (DN) in eNOS-/- db/db mice.
Zhang MZ, Wang S, Yang S, Yang H, Fan X, Takahashi T, Harris RC (2012) Am J Physiol Renal Physiol 302(4): F433-8
Citation ⋅ 22114203 (PubMed) PMC3289417 (PubMed Central)14. Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice.
Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, Yin H, Yang S, Harris RC (2011) J Clin Invest 121(7): 2845-54
Citation ⋅ 21701066 (PubMed) PMC3223841 (PubMed Central)15. Integrin alpha1beta1 regulates epidermal growth factor receptor activation by controlling peroxisome proliferator-activated receptor gamma-dependent caveolin-1 expression.
Chen X, Whiting C, Borza C, Hu W, Mont S, Bulus N, Zhang MZ, Harris RC, Zent R, Pozzi A (2010) Mol Cell Biol 30(12): 3048-58
Citation ⋅ 20368353 (PubMed) PMC2876688 (PubMed Central)16. Sirt1 activation protects the mouse renal medulla from oxidative injury.
He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, Yang HC, Fogo AB, Zent R, Harris RC, Breyer MD, Hao CM (2010) J Clin Invest 120(4): 1056-68
Citation ⋅ 20335659 (PubMed) PMC2846063 (PubMed Central)17. Assessing the application of tissue microarray technology to kidney research.
Zhang MZ, Su Y, Yao B, Zheng W, Decaestecker M, Harris RC (2010) J Histochem Cytochem 58(5): 413-20
Citation ⋅ 20086233 (PubMed) PMC2857813 (PubMed Central)18. Intrarenal dopamine attenuates deoxycorticosterone acetate/high salt-induced blood pressure elevation in part through activation of a medullary cyclooxygenase 2 pathway.
Yao B, Harris RC, Zhang MZ (2009) Hypertension 54(5): 1077-83
Citation ⋅ 19770404 (PubMed) PMC2782522 (PubMed Central)19. Inhibition of 11beta-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans.
Zhang MZ, Xu J, Yao B, Yin H, Cai Q, Shrubsole MJ, Chen X, Kon V, Zheng W, Pozzi A, Harris RC (2009) J Clin Invest 119(4): 876-85
Citation ⋅ 19307727 (PubMed) PMC2662561 (PubMed Central)20. Intrarenal dopaminergic system regulates renin expression.
Zhang MZ, Yao B, Fang X, Wang S, Smith JP, Harris RC (2009) Hypertension 53(3): 564-70
Citation ⋅ 19139376 (PubMed) PMC2680004 (PubMed Central)21. Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase.
Yao B, Xu J, Harris RC, Zhang MZ (2008) Am J Physiol Renal Physiol 294(2): F433-9
Citation ⋅ 18057186 (PubMed)22. ErbB4 isoforms selectively regulate growth factor induced Madin-Darby canine kidney cell tubulogenesis.
Zeng F, Zhang MZ, Singh AB, Zent R, Harris RC (2007) Mol Biol Cell 18(11): 4446-56
Citation ⋅ 17761534 (PubMed) PMC2043549 (PubMed Central)23. Characterization of a putative intrarenal serotonergic system.
Xu J, Yao B, Fan X, Langworthy MM, Zhang MZ, Harris RC (2007) Am J Physiol Renal Physiol 293(5): F1468-75
Citation ⋅ 17715266 (PubMed)24. Overexpression of cyclooxygenase-2 predisposes to podocyte injury.
Cheng H, Wang S, Jo YI, Hao CM, Zhang M, Fan X, Kennedy C, Breyer MD, Moeckel GW, Harris RC (2007) J Am Soc Nephrol 18(2): 551-9
Citation ⋅ 17202413 (PubMed)25. Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT(1) and AT(2) receptors.
Zhang MZ, Yao B, Cheng HF, Wang SW, Inagami T, Harris RC (2006) Proc Natl Acad Sci U S A 103(43): 16045-50
Citation ⋅ 17043228 (PubMed) PMC1635124 (PubMed Central)26. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice.
Zhao HJ, Wang S, Cheng H, Zhang MZ, Takahashi T, Fogo AB, Breyer MD, Harris RC (2006) J Am Soc Nephrol 17(10): 2664-9
Citation ⋅ 16971655 (PubMed) PMC4618687 (PubMed Central)27. Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake.
Yao B, Xu J, Qi Z, Harris RC, Zhang MZ (2006) Am J Physiol Renal Physiol 291(2): F368-74
Citation ⋅ 16597606 (PubMed)28. Nitric oxide stimulates cyclooxygenase-2 in cultured cTAL cells through a p38-dependent pathway.
Cheng HF, Zhang MZ, Harris RC (2006) Am J Physiol Renal Physiol 290(6): F1391-7
Citation ⋅ 16380459 (PubMed)29. Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition.
Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC (2005) Nephron Exp Nephrol 101(3): e75-85
Citation ⋅ 15995341 (PubMed)30. Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney.
Yao B, Harris RC, Zhang MZ (2005) Am J Physiol Regul Integr Comp Physiol 288(6): R1767-73
Citation ⋅ 15718388 (PubMed)31. Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems.
Zhang MZ, Yao B, McKanna JA, Harris RC (2005) Am J Physiol Renal Physiol 288(4): F840-5
Citation ⋅ 15613619 (PubMed)32. Lithium treatment inhibits renal GSK-3 activity and promotes cyclooxygenase 2-dependent polyuria.
Rao R, Zhang MZ, Zhao M, Cai H, Harris RC, Breyer MD, Hao CM (2005) Am J Physiol Renal Physiol 288(4): F642-9
Citation ⋅ 15585669 (PubMed)33. Cyclooxygenase-2 and the renal renin-angiotensin system.
Harris RC, Zhang MZ, Cheng HF (2004) Acta Physiol Scand 181(4): 543-7
Citation ⋅ 15283769 (PubMed)34. Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney.
Schneider A, Zhang Y, Zhang M, Lu WJ, Rao R, Fan X, Redha R, Davis L, Breyer RM, Harris R, Guan Y, Breyer MD (2004) Kidney Int 65(4): 1205-13
Citation ⋅ 15086459 (PubMed)35. PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells.
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 (2004) Proc Natl Acad Sci U S A 101(8): 2311-6
Citation ⋅ 14983006 (PubMed) PMC356947 (PubMed Central)36. Regulation of cyclooxygenase expression by vasopressin in rat renal medulla.
Zhang MZ, Sanchez Lopez P, McKanna JA, Harris RC (2004) Endocrinology 145(3): 1402-9
Citation ⋅ 14684611 (PubMed)37. Regulation of renal cortical cyclooxygenase-2 in young rats.
Zhang MZ, Wang SW, Cheng H, Zhang Y, McKanna JA, Harris RC (2003) Am J Physiol Renal Physiol 285(5): F881-8
Citation ⋅ 12851252 (PubMed)38. Prostaglandins that increase renin production in response to ACE inhibition are not derived from cyclooxygenase-1.
Cheng HF, Wang SW, Zhang MZ, McKanna JA, Breyer R, Harris RC (2002) Am J Physiol Regul Integr Comp Physiol 283(3): R638-46
Citation ⋅ 12184998 (PubMed)39. Mineralocorticoid regulation of cyclooxygenase-2 expression in rat renal medulla.
Zhang MZ, Hao CM, Breyer MD, Harris RC, McKanna JA (2002) Am J Physiol Renal Physiol 283(3): F509-16
Citation ⋅ 12167602 (PubMed)40. Cyclooxygenase-2 inhibitor blocks expression of mediators of renal injury in a model of diabetes and hypertension.
Cheng HF, Wang CJ, Moeckel GW, Zhang MZ, McKanna JA, Harris RC (2002) Kidney Int 62(3): 929-39
Citation ⋅ 12164875 (PubMed)41. Genetic deletion of COX-2 prevents increased renin expression in response to ACE inhibition.
Cheng HF, Wang JL, Zhang MZ, Wang SW, McKanna JA, Harris RC (2001) Am J Physiol Renal Physiol 280(3): F449-56
Citation ⋅ 11181406 (PubMed)42. Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride.
Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC (2000) J Clin Invest 106(5): 681-8
Citation ⋅ 10974021 (PubMed) PMC381289 (PubMed Central)43. Nitric oxide regulates renal cortical cyclooxygenase-2 expression.
Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC (2000) Am J Physiol Renal Physiol 279(1): F122-9
Citation ⋅ 10894794 (PubMed)44. Interactions of the renin-angiotensin system and neuronal nitric oxide synthase in regulation of cyclooxygenase-2 in the macula densa.
Harris RC, Cheng H, Wang J, Zhang M, McKanna JA (2000) Acta Physiol Scand 168(1): 47-51
Citation ⋅ 10691779 (PubMed)45. Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids.
Zhang MZ, Harris RC, McKanna JA (1999) Proc Natl Acad Sci U S A 96(26): 15280-5
Citation ⋅ 10611376 (PubMed) PMC24811 (PubMed Central)46. Angiotensin II attenuates renal cortical cyclooxygenase-2 expression.
Cheng HF, Wang JL, Zhang MZ, Miyazaki Y, Ichikawa I, McKanna JA, Harris RC (1999) J Clin Invest 103(7): 953-61
Citation ⋅ 10194467 (PubMed) PMC408259 (PubMed Central)47. Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN).
Zhang MC, He L, Giro M, Yong SL, Tiller GE, Davidson JM (1999) J Biol Chem 274(2): 981-6
Citation ⋅ 9873040 (PubMed)48. Selective increase of cyclooxygenase-2 expression in a model of renal ablation.
Wang JL, Cheng HF, Zhang MZ, McKanna JA, Harris RC (1998) Am J Physiol 275(4): F613-22
Citation ⋅ 9755133 (PubMed)49. Prostaglandins in macula densa function.
Harris RC, Wang JL, Cheng HF, Zhang MZ, McKanna JA (1998) Kidney Int Suppl 67(): S49-52
Citation ⋅ 9736253 (PubMed)50. Constitutive expression of cyclooxygenase-2 in rat vas deferens.
McKanna JA, Zhang MZ, Wang JL, Cheng H, Harris RC (1998) Am J Physiol 275(1): R227-33
Citation ⋅ 9688983 (PubMed)51. Cyclooxygenase-2 in rat nephron development.
Zhang MZ, Wang JL, Cheng HF, Harris RC, McKanna JA (1997) Am J Physiol 273(6 Pt 2): F994-1002
Citation ⋅ 9435689 (PubMed)52. 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.
Melzer P, Zhang MZ, McKanna JA (1997) Neuroscience 80(2): 459-72
Citation ⋅ 9284349 (PubMed)53. Gliogenesis in postnatal rat optic nerve: LC1 + microglia and S100-beta + astrocytes.
Zhang MZ, McKanna JA (1997) Brain Res Dev Brain Res 101(1-2): 27-36
Citation ⋅ 9263577 (PubMed)54. 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.
Sakai M, Zhang M, Homma T, Garrick B, Abraham JA, McKanna JA, Harris RC (1997) J Clin Invest 99(9): 2128-38
Citation ⋅ 9151785 (PubMed) PMC508043 (PubMed Central)55. Immunohistochemical localization of lipocortin 1 in rat brain is sensitive to pH, freezing, and dehydration.
McKanna JA, Zhang MZ (1997) J Histochem Cytochem 45(4): 527-38
Citation ⋅ 9111231 (PubMed)