Phosphodiesterase 5 inhibition ameliorates angiontensin II-induced podocyte dysmotility via the protein kinase G-mediated downregulation of TRPC6 activity

American Journal of Physiology - Renal Physiology

Volumn 306, Issue 12, 2014, Pages

  Hall, Gentzon ^a   Rowell, Janelle ^b   Farinelli, Federica ^b   Gbadegesin, Rasheed A ^a   Lavin, Peter ^c   Wu, Guanghong ^a   Homstad, Alison ^a   Malone, Andrew ^a   Lindsey, Thomas ^a   Jiang, Ruiji ^a   Spurney, Robert ^a   Tomaselli, Gordon F ^b   Kass, David A ^b   Winn, Michelle P ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c ADELAIDE AND MEATH HOSPITAL   (Ireland)

Author keywords

Calcineurin; Phosphodiesterase 5; Podocyte; Protein kinase G; Transient receptor potential cation channel isotype 6

Indexed keywords

8 BROMO CYCLIC GMP; ANGIOTENSIN II; CALCINEURIN; CYCLIC GMP DEPENDENT PROTEIN KINASE; GUANYLATE CYCLASE; N ACETYLPENICILLAMINE; PHOSPHODIESTERASE V; PHOSPHODIESTERASE V INHIBITOR; TRANSIENT RECEPTOR POTENTIAL CHANNEL 6;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL ACTIVITY; CELL MOTILITY; CELL STIMULATION; CONTROLLED STUDY; DEPHOSPHORYLATION; DOWN REGULATION; GENE OVEREXPRESSION; HEK293 CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; NONHUMAN; PODOCYTE; PODOCYTE DYSMOTILITY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; WOUND HEALING;

CALCINEURIN; PHOSPHODIESTERASE 5; PODOCYTE; PROTEIN KINASE G; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL ISOTYPE 6;

ANGIOTENSIN II; ANIMALS; CALCIUM SIGNALING; CELL MOVEMENT; CELLS, CULTURED; CYCLIC GMP-DEPENDENT PROTEIN KINASES; DOWN-REGULATION; HEK293 CELLS; HUMANS; MICE; MICE, INBRED STRAINS; MODELS, ANIMAL; NFATC TRANSCRIPTION FACTORS; PHOSPHODIESTERASE 5 INHIBITORS; PHOSPHORIC MONOESTER HYDROLASES; PHOSPHORYLATION; PODOCYTES; SIGNAL TRANSDUCTION; TRPC CATION CHANNELS;

EID: 84902683099     PISSN: 1931857X     EISSN: 15221466     Source Type: Journal    
DOI: 10.1152/ajprenal.00212.2013     Document Type: Article

References (47)

1. Akilesh S, Suleiman H, Yu H, Stander MC, Lavin P, Gbadegesin R, Antignac C, Pollak M, Kopp JB, Winn MP, Shaw AS. Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis. J Clin Invest 121: 4127-4137, 2011.
2. Asanuma K, Yanagida-Asanuma E, Faul C, Tomino Y, Kim K, Mundel P. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. Nat Cell Biol 8: 485-491, 2006.
3. Bessay EP, Zoraghi R, Blount MA, Grimes KA, Beasley A, Francis SH, Corbin JD. Phosphorylation of phosphodiesterase-5 is promoted by a conformational change induced by sildenafil, vardenafil, or tadalafil. Front Biosci 12: 1899-1910, 2007.
4. Browner NC, Dey NB, Bloch KD, Lincoln TM. Regulation of cGMPdependent protein kinase expression by soluble guanylyl cyclase in vascular smooth muscle cells. J Biol Chem 279: 46631-46636, 2004.
5. Dandapani SV, Sugimoto H, Matthews BD, Kolb RJ, Sinha S, Gerszten RE, Zhou J, Ingber DE, Kalluri R, Pollak MR. Alpha-actinin-4 is required for normal podocyte adhesion. J Biol Chem 282: 467-477, 2007.
6. Ding X, He Z, Shi Y, Wang Q, Wang Y. Targeting TRPC6 channels in oesophageal carcinoma growth. Exp Opin Ther Targets 14: 513-527, 2010.
7. Eckel J, Lavin PJ, Finch EA, Mukerji N, Burch J, Gbadegesin R, Wu G, Bowling B, Byrd A, Hall G, Sparks M, Zhang ZS, Homstad A, Barisoni L, Birbaumer L, Rosenberg P, Winn MP. TRPC6 enhances angiotensin II-induced albuminuria. J Am Soc Nephrol 22: 526-535, 2011.
8. Fang L, Radovits T, Szabo G, Mozes MM, Rosivall L, Kokeny G. Selective phosphodiesterase-5 (PDE-5) inhibitor vardenafil ameliorates renal damage in type 1 diabetic rats by restoring cyclic 3′,5′ guanosine monophosphate (cGMP) level in podocytes. Nephrol Dial Transplant 28: 1751-1761, 2013.
9. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14: 931-938, 2008.
10. Francis SH, Bessay EP, Kotera J, Grimes KA, Liu L, Thompson WJ, Corbin JD. Phosphorylation of isolated human phosphodiesterase-5 regulatory domain induces an apparent conformational change and increases cGMP binding affinity. J Biol Chem 277: 47581-47587, 2002.
11. Giordano D, De Stefano ME, Citro G, Modica A, Giorgi M. Expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in mouse tissues and cell lines using an antibody against the enzyme amino-terminal domain. Biochim Biophys Acta 1539: 16-27, 2001.
12. Graham S, Gorin Y, Abboud HE, Ding M, Lee DY, Shi H, Ding Y, Ma R. Abundance of TRPC6 protein in glomerular mesangial cells is decreased by ROS and PKC in diabetes. Am J Physiol Cell Physiol 301: C304-C315, 2011.
13. Hofmann F, Feil R, Kleppisch T, Schlossmann J. Function of cGMPdependent protein kinases as revealed by gene deletion. Physiol Rev 86: 1-23, 2006.
14. Hsu HH, Hoffmann S, Endlich N, Velic A, Schwab A, Weide T, Schlatter E, Pavenstadt H. Mechanisms of angiotensin II signaling on cytoskeleton of podocytes. J Mol Med 86: 1379-1394, 2008.
15. Kanetsuna Y, Takahashi K, Nagata M, Gannon MA, Breyer MD, Harris RC, Takahashi T. Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice. Am J Pathol 170: 1473-1484, 2007.
16. Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodriguez-Perez JC, Allen PG, Beggs AH, Pollak MR. Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 24: 251-256, 2000.
17. Kim JY, Saffen D. Activation of M1 muscarinic acetylcholine receptors stimulates the formation of a multiprotein complex centered on TRPC6 channels. J Biol Chem 280: 32035-32047, 2005.
18. Kinoshita H, Kuwahara K, Nishida M, Jian Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K, Nakao K. Inhibition of TRPC6 channel activity contributes to the antihypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart. Circ Res 106: 1849-1860, 2010.
19. Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF, Kass DA. Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation. Novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol 48: 713-724, 2010.
20. Kuwahara K, Wang Y, McAnally J, Richardson JA, Bassel-Duby R, Hill JA, Olson EN. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Invest 116: 3114-3126, 2006.
21. Kwon Y, Hofmann T, Montell C. Integration of phosphoinositide-and calmodulin-mediated regulation of TRPC6. Mol Cell 25: 491-503, 2007.
22. Lea JP, Jin SG, Roberts BR, Shuler MS, Marrero MB, Tumlin JA. Angiotensin II stimulates calcineurin activity in proximal tubule epithelia through AT-1 receptor-mediated tyrosine phosphorylation of the PLC-γ1 isoform. J Am Soc Nephrol 13: 1750-1756, 2002.
23. Lewko B, Golos M, Latawiec E, Angielski S, Stepinski J. Regulation of cGMP synthesis in cultured podocytes by vasoactive hormones. J Physiol Pharmacol 57: 599-610, 2006.
24. Lincoln TM, Dey N, Sellak H. Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91: 1421-1430, 2001.
25. Lu TC, He JC, Wang ZH, Feng X, Fukumi-Tominaga T, Chen N, Xu J, Iyengar R, Klotman PE. HIV-1 Nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein. J Biol Chem 283: 8173-8182, 2008.
26. Lu W, Ran P, Zhang D, Peng G, Li B, Zhong N, Wang J. Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle. Am J Physiol Cell Physiol 298: C114-C123, 2010.
27. Ma H, Togawa A, Soda K, Zhang J, Lee S, Ma M, Yu Z, Ardito T, Czyzyk J, Diggs L, Joly D, Hatakeyama S, Kawahara E, Holzman L, Guan JL, Ishibe S. Inhibition of podocyte FAK protects against proteinuria and foot process effacement. J Am Soc Nephrol 21: 1145-1156, 2010.
28. Moller CC, Wei C, Altintas MM, Li J, Greka A, Ohse T, Pippin JW, Rastaldi MP, Wawersik S, Schiavi S, Henger A, Kretzler M, Shankland SJ, Reiser J. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J Am Soc Nephrol 18: 29-36, 2007.
29. Mundel P, Gambaryan S, Bachmann S, Koesling D, Kriz W. Immunolocalization of soluble guanylyl cyclase subunits in rat kidney. Histochem Cell Biol 103: 75-79, 1995.
30. Nijenhuis T, Sloan AJ, Hoenderop JG, Flesche J, van Goor H, Kistler AD, Bakker M, Bindels RJ, de Boer RA, Moller CC, Hamming I, Navis G, Wetzels JF, Berden JH, Reiser J, Faul C, van der Vlag J. Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway. Am J Pathol 179: 1719-1732, 2011.
31. Nishida M, Watanabe K, Sato Y, Nakaya M, Kitajima N, Ide T, Inoue R, Kurose H. Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition. J Biol Chem 285: 13244-13253, 2010.
32. Onohara N, Nishida M, Inoue R, Kobayashi H, Sumimoto H, Sato Y, Mori Y, Nagao T, Kurose H. TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. EMBO J 25: 5305-5316, 2006.
33. Reiser J, Oh J, Shirato I, Asanuma K, Hug A, Mundel TM, Honey K, Ishidoh K, Kominami E, Kreidberg JA, Tomino Y, Mundel P. Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and α3 integrin. J Biol Chem 279: 34827-34832, 2004.
34. Rivero-Vilches FJ, de Frutos S, Saura M, Rodriguez-Puyol D, Rodriguez-Puyol M. Differential relaxing responses to particulate or soluble guanylyl cyclase activation on endothelial cells: a mechanism dependent on PKG-Iα activation by NO/cGMP. Am J Physiol Cell Physiol 285: C891-C898, 2003.
35. Seo K, Rainer PP, Lee DI, Hao S, Bedja D, Birnbaumer L, Cingolani OH, Kass DA. Hyperactive adverse mechanical-stress responses in dystrophic heart are coupled to TRPC6 and blocked by cGMP-PKG modulation. Circ Res 114: 823-832, 2014.
36. Seo K, Rainer PP, Shalkey Hahn V, Lee DI, Jo SH, Andersen A, Liu T, Xu X, Willette RN, Lepore JJ, Marino JP Jr, Birnbaumer L, Schnackenberg CG, Kass DA. Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proc Natl Acad Sci USA 111: 1551-1556, 2014.
37. Suzuki E, Nishimatsu H, Satonaka H, Walsh K, Goto A, Omata M, Fujita T, Nagai R, Hirata Y. Angiotensin II induces myocyte enhancer factor 2-and calcineurin/nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes. Circ Res 90: 1004-1011, 2002.
38. Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R. Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol 586: 4209-4223, 2008.
39. Terada Y, Tomita K, Nonoguchi H, Marumo F. Polymerase chain reaction localization of constitutive nitric oxide synthase and soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments. J Clin Invest 90: 659-665, 1992.
40. Thilo F, Liu Y, Loddenkemper C, Schuelein R, Schmidt A, Yan Z, Zhu Z, Zakrzewicz A, Gollasch M, Tepel M. VEGF regulates TRPC6 channels in podocytes. Nephrol Dial Transplant 27: 921-929, 2012.
41. Turner JD, Thomas AP, Reeves JP, Hantash BM. Calcineurin activation by slow calcium release from intracellular stores suppresses protein kinase C regulation of L-type calcium channels in L6 cells. Cell Calcium 46: 242-247, 2009.
42. Urban N, Hill K, Wang L, Kuebler WM, Schaefer M. Novel pharmacological TRPC inhibitors block hypoxia-induced vasoconstriction. Cell Calcium 51: 194-206, 2012.
43. Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308: 1801-1804, 2005.
44. 2+. Handb Exp Pharmacol: 527-540, 2007.
45. Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, Tigno DD, Thistlethwaite PA, Rubin LJ, Yuan JX. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 101: 13861-13866, 2004.
46. Yuen DA, Stead BE, Zhang Y, White KE, Kabir MG, Thai K, Advani SL, Connelly KA, Takano T, Zhu L, Cox AJ, Kelly DJ, Gibson IW, Takahashi T, Harris RC, Advani A. eNOS deficiency predisposes podocytes to injury in diabetes. J Am Soc Nephrol 23: 1810-1823, 2012.
47. Zhang Q, Shi SF, Zhu L, Lv JC, Liu LJ, Chen YQ, Zhang H, Wang HY. Tacrolimus improves the proteinuria remission in patients with refractory IgA nephropathy. Am J Nephrol 35: 312-320, 2012.