Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-β

American Journal of Respiratory and Critical Care Medicine

Volumn 186, Issue 8, 2012, Pages 740-751

  Kottmann, Robert Matthew ^a   Kulkarni, Ajit A ^a   Smolnycki, Katie A ^a   Lyda, Elizabeth ^a   Dahanayake, Thinesh ^a   Salibi, Rami ^a   Honnons, Sylvie ^a   Jones, Carolyn ^b   Isern, Nancy G ^c   Hu, Jian Z ^c   Nathan, Steven D ^d   Grant, Geraldine ^e   Phipps, Richard P ^a,b   Sime, Patricia J ^a,b  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b UNIVERSITY OF ROCHESTER   (United States)

^c PACIFIC NORTHWEST NATIONAL LABORATORY   (United States)

^d INOVA FAIRFAX HOSPITAL   (United States)

^e GEORGE MASON UNIVERSITY   (United States)

Author keywords

Hypoxia inducible factor 1 ; Idiopathic pulmonary fibrosis; Lactate; Lactate dehydrogenase; Myofibroblast

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; CALPONIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LACTATE DEHYDROGENASE 5; LACTIC ACID; OXIDOREDUCTASE; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG;

ARTICLE; CELL DIFFERENTIATION; CELL LYSATE; CELL METABOLISM; CONCENTRATION (PARAMETERS); ENZYME ACTIVATION; FIBROSING ALVEOLITIS; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; HUMAN TISSUE; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; LUNG FIBROBLAST; METABOLOMICS; MOLECULAR CLONING; MYOFIBROBLAST; PH; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTON NUCLEAR MAGNETIC RESONANCE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

CASE-CONTROL STUDIES; CELL DIFFERENTIATION; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; HYDROGEN-ION CONCENTRATION; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IDIOPATHIC PULMONARY FIBROSIS; ISOENZYMES; L-LACTATE DEHYDROGENASE; LACTIC ACID; MAGNETIC RESONANCE SPECTROSCOPY; MYOFIBROBLASTS; TRANSFORMING GROWTH FACTOR BETA; UP-REGULATION;

EID: 84867604212     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201201-0084OC     Document Type: Article

References (38)

1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788-824.
2. Kottmann RM, Hogan CM, Phipps RP, Sime PJ. Determinants of initiation and progression of idiopathic pulmonary fibrosis. Respirology 2009;14:917-933.
3. Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest 1997;100:768-776. (Pubitemid 27371693)
4. Bartram U, Speer CP. The role of transforming growth factor beta in lung development and disease. Chest 2004;125:754-765. (Pubitemid 38223659)
5. Kelly M, Kolb M, Bonniaud P, Gauldie J. Re-evaluation of fibrogenic cytokines in lung fibrosis. Curr Pharm Des 2003;9:39-49. (Pubitemid 36131704)
6. Wipff PJ, Hinz B. Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship. Eur J Cell Biol 2008;87:601-615.
7. Khalil N. TGF-beta: From latent to active. Microbes Infect 1999;1:1255-1263.
8. Aluwihare P, Munger JS. What the lung has taught us about latent TGFbeta activation. Am J Respir Cell Mol Biol 2008;39:499-502.
9. Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci 2003;116:217-224. (Pubitemid 36163863)
10. Lawrence DA, Pircher R, Jullien P. Conversion of a high molecular weight latent beta-TGF from chicken embryo fibroblasts into a low molecular weight active beta-TGF under acidic conditions. Biochem Biophys Res Commun 1985;133:1026-1034. (Pubitemid 16142882)
11. Hu JZ, Rommereim DN, Minard KR, Woodstock A, Harrer BJ, Wind RA, Phipps RP, Sime PJ. Metabolomics in lung inflammation:A high-resolution (1)h NMR study of mice exposed to silica dust. Toxicol Mech Methods 2008;18:385-398. (Pubitemid 351883379)
12. Drent M, Cobben NA, Henderson RF, Wouters EF, van Dieijen-Visser M. Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation. Eur Respir J 1996;9:1736-1742. (Pubitemid 26271162)
13. Lott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clin Chem 1980;26:1241-1250. (Pubitemid 10035220)
14. Valentine WN, Tanaka KR, Paglia DE. Hemolytic anemias and erythrocyte enzymopathies. Ann Intern Med 1985;103:245-257. (Pubitemid 15000580)
15. Tiu RV, Mountantonakis SE, Dunbar AJ, Schreiber MJ Jr. Tumor lysis syndrome. Semin Thromb Hemost 2007;33:397-407. (Pubitemid 46878112)
16. Zhang SX, Miller JJ, Stolz DB, Serpero LD, Zhao W, Gozal D, Wang Y. Type I epithelial cells are the main target of whole-body hypoxic preconditioning in the lung. Am J Respir Cell Mol Biol 2009;40:332-339.
17. Emad A, Emad V. The value of BAL fluid LDH level in differentiating benign from malignant solitary pulmonary nodules. J Cancer Res Clin Oncol 2008;134:489-493. (Pubitemid 351322385)
18. Rossignol F, Solares M, Balanza E, Coudert J, Clottes E. Expression of lactate dehydrogenase a and b genes in different tissues of rats adapted to chronic hypobaric hypoxia. J Cell Biochem 2003;89:67-79. (Pubitemid 36459099)
19. Giatromanolaki A, Koukourakis MI, Pezzella F, Sivridis E, Turley H, Harris AL, Gatter KC. Lactate dehydrogenase 5 expression in non-Hodgkin B-cell lymphomas is associated with hypoxia regulated proteins. Leuk Lymphoma 2008;49:2181-2186.
20. Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, Harris AL. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer 2003;89:877-885. (Pubitemid 37175811)
21. Schmid SA, Gaumann A, Wondrak M, Eckermann C, Schulte S, Mueller-Klieser W, Wheatley DN, Kunz-Schughart LA. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-beta1. Exp Cell Res 2007;313:2531-2549. (Pubitemid 46992738)
22. Kottmann RM, Smolnycki KA, Phipps RP, Sime PJ. Physiologic concentrations of lactate activate TGFb in a pH dependent manner and drive myofibroblast differentiation [abstract]. Proc Am Thorac Soc 2010;7:A3521.
23. Kottmann RM, Smolnycki KA, Lyda E, Dahanayake T, Jones C, Phipps RP, Sime PJ. Transforming growth factor beta up-regulates lactate dehydrogenase expression in primary human lung fibroblasts: implications for cellular metabolism [abstract]. Proc Am Thorac Soc 2010;7:A3520.
24. Dahanayake TM, Smolnycki K, Xu HD, Sime PJ, Kottmann RM. LDH5 expression in idiopathic pulmonary fibrosis [abstract]. Proc Am Thorac Soc 2010;7:A3503.
25. Kottmann RM, Smolnycki KA, Lyda B, Dahanayake T, Hu JZ, Phipps RP, Sime PJ. Metabolomics identifies lactic acid as a potential activator of TGF-β: implications for the contribution of cellular metabolism to the progression of pulmonary fibrosis. Presented at the International Colloquium on Lung and Airways Fibrosis. October, 2010, Busselton, Australia. Abstract.
26. Dahayanake T, Smolnycki KA, Phipps RP, Sime PJ, Kottmann RM. LDH5 expression in organizing pneumonia: lactic acid upregulates IL-6 and PGE-2 expression in primary human lung fibroblasts and FGF and PDGF in human lung epithelial cells [abstract]. Am J Respir Crit Care Med 2011;183:A3483.
27. Baglole CJ, Reddy SY, Pollock SJ, Feldon SE, Sime PJ, Smith TJ, Phipps RP. Isolation and phenotypic characterization of lung fibroblasts. Methods Mol Med 2005;117:115-127.
28. Ferguson HE, Kulkarni A, Lehmann GM, Garcia-Bates TM, Thatcher TH, Huxlin KR, Phipps RP, Sime PJ. Electrophilic peroxisome proliferator-activated receptor-gamma ligands have potent antifibrotic effects in human lung fibroblasts. Am J Respir Cell Mol Biol 2009;41:722-730.
29. Wind RA, Hu JZ, Rommereim DN. High-resolution (1)h NMR spectroscopy in organs and tissues using slow magic angle spinning. Magn Reson Med 2001;46:213-218. (Pubitemid 32703265)
30. Jurukovski V, Dabovic B, Todorovic V, Chen Y, Rifkin DB. Methods for measuring TGF-b using antibodies, cells, and mice. Methods Mol Med 2005;117:161-175.
31. Ferguson HE, Kulkarni A, Lehmann GM, Garcia-Bates TM, Thatcher TH, Huxlin KR, Phipps RP, Sime PJ. Electrophilic peroxisome proliferator activated receptor-gamma ligands have potent antifibrotic effects in human lung fibroblasts. Am J Respir Cell Mol Biol 2009.41:722-730.
32. Kolb M, Margetts PJ, Sime PJ, Gauldie J. Proteoglycans decorin and biglycan differentially modulate TGF-beta-mediated fibrotic responses in the lung. Am J Physiol 2001;280:L1327-L1334.
33. Kulkarni AA, Thatcher TH, Olsen KC, Maggirwar SB, Phipps RP, Sime PJ. PPAR-γ ligands repress TGFβ-induced myofibroblast differentiation by targeting the PI3K/Akt pathway: implications for therapy of fibrosis. PLoS ONE 2011;6:e15909.
34. Jiang BH, Rue E, Wang GL, Roe R, Semenza GL. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem 1996;271:17771-17778. (Pubitemid 26250751)
35. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996;16:4604-4613. (Pubitemid 26272112)
36. Gumienny TL, Padgett RW. The other side of TGF-beta superfamily signal regulation: thinking outside the cell. Trends Endocrinol Metab 2002;13:295-299. (Pubitemid 36733959)
37. Zhu HJ, Burgess AW. Regulation of transforming growth factor-beta signaling. Mol Cell Biol Res Commun 2001;4:321-330. (Pubitemid 33098102)
38. Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001;12:S15-S19. (Pubitemid 32119049)