Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis.

[en] BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder of unknown origin, which ultimately leads to death. Several growth factors such as IGFs (insulin-like-growth factor) and IGFBPs (insulin like growth factor binding proteins) seem to take part to the pathogenesis. We evaluated IGFs and IGFBPs in serum from patients with IPF and healthy subjects including 24 untreated IPF and 26 IPF receiving anti-fibrotic therapy and to compare them with healthy subjects. METHODS: Serum of 50 idiopathic pulmonary fibrosis and 55 healthy subjects (HS) were analysed by ELISA for IGFs and IGFBPs, TGF-beta and KL-6, the latter being tested as positive control in IPF. RESULTS: Serum levels of IGFBP-1 and IGFBP-2 and KL-6 were significantly higher in the IPF group than in the healthy subjects (p < 0.05, p < 0.001 and p < 0.0001 respectively) while the picture was inversed regarding IGFs. By contrast there was no significant difference between the groups with respect to TGF-beta. IGFBP-2 was significantly reduced in the patients with specific anti-fibrotic therapy pirfenidone and nintedanib compared to untreated patients (p < 0.05) but still significantly elevated in comparison to HS (p < 0.001). CONCLUSION: Serum IGFBP-1 and -2 are increased in idiopathic pulmonary fibrosis and IGFBP-2 may be reduced by anti-fibrosing therapy. IGFBPs may be promising biomarkers in IPF.

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

GUIOT, Julien ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie

Bondue, B.

HENKET, Monique ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie

CORHAY, Jean-Louis ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie

LOUIS, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie

Language :

English

Title :

Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis.

Publication date :

23 May 2016

Journal title :

BMC Pulmonary Medicine

eISSN :

1471-2466

Publisher :

BioMed Central, United Kingdom

Volume :

Issue :

Pages :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877734/pdf/12890_2016_Article_249.pdf

Available on ORBi :

since 27 June 2016

Statistics

Number of views

111 (11 by ULiège)

Number of downloads

62 (1 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Ganesh Raghu HRC, Egan JJ, Martinez FJ, Juergen B, Brown KK, Colby TV, Jean-François C, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Julio A, Demosthenes B, Carlos C, Ulrich C, Masahito E, Hansell DM, Takeshi J, Dong Soon K, King TE Jr, Yasuhiro K, Jeffrey M, Müller NL, Nicholson AG, Luca R, Moisés S, Dudden RF, Griss BS, Protzko SL, Schünemann HJ. 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(6):788-824.
Wilson KC, Raghu G. The 2015 guidelines for idiopathic pulmonary fibrosis: an important chapter in the evolution of the management of patients with IPF. Eur Respir J. 2015;46(4):883-6.
Spagnolo P, Tonelli R, Cocconcelli E, Stefani A, Richeldi L. Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges. Multidiscip Respir Med. 2012;7(1):42.
Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Hirohashi N, Tanigawa K, et al. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med. 2014;108(7):1031-9.
Samukawa T, Hamada T, Uto H, Yanagi M, Tsukuya G, Nosaki T, et al. The elevation of serum napsin A in idiopathic pulmonary fibrosis, compared with KL-6, surfactant protein-A and surfactant protein-D. BMC Pulm Med. 2012;12:55.
Ten Klooster L, van Moorsel CH, Kwakkel-van Erp JM, van Velzen-Blad H, Grutters JC. IgA in serum: An old acquaintance as a new prognostic biomarker in Idiopathic Pulmonary Fibrosis. Clin Exp Immunol. 2015;181(2):357-61.
Tajiri M, Okamoto M, Fujimoto K, Johkoh T, Ono J, Tominaga M, et al. Serum level of periostin can predict long-term outcome of idiopathic pulmonary fibrosis. Respir Investig. 2015;53(2):73-81.
Ley B, Brown KK, Collard HR. Molecular biomarkers in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2014;307(9):L681-91.
Zhang Y, Kaminski N. Biomarkers in idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 2012;18(5):441-6.
Hirota N, Ito T, Miyazaki S, Ebina M, Homma S. Gene expression profiling of lung myofibroblasts reveals the anti-fibrotic effects of cyclosporine. Tohoku J Exp Med. 2014;233(4):283-93.
Ruan W, Ying K. Abnormal expression of IGF-binding proteins, an initiating event in idiopathic pulmonary fibrosis? Pathol Res Pract. 2010;206(8):537-43.
Chadelat K, Boule M, Corroyer S, Fauroux B, Delaisi B, Tournier G, et al. Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease. Eur Respir J. 1998;11(6):1329-36.
Mouhieddine OB, Cazals V, Maitre B, Le Bouc Y, Chadelat K, Clement A. Insulin-like growth factor-II (IGF-II), type 2 IGF receptor, and IGF-binding protein-2 gene expression in rat lung alveolar epithelial cells: relation to proliferation. Endocrinology. 1994;135(1):83-91.
Cazals V, Mouhieddine B, Maitre B, Le Bouc Y, Chadelat K, Brody JS, et al. Insulin-like growth factors, their binding proteins, and transforming growth factor-beta 1 in oxidant-arrested lung alveolar epithelial cells. J Biol Chem. 1994;269(19):14111-7.
Mouhieddine OB, Cazals V, Kuto E, Le Bouc Y, Clement A. Glucocorticoidinduced growth arrest of lung alveolar epithelial cells is associated with increased production of insulin-like growth factor binding protein-2. Endocrinology. 1996;137(1):287-95.
Duan C. Specifying the cellular responses to IGF signals: roles of IGF-binding proteins. J Endocrinol. 2002;175(1):41-54.
Perks CM, Newcomb PV, Norman MR, Holly JM. Effect of insulin-like growth factor binding protein-1 on integrin signalling and the induction of apoptosis in human breast cancer cells. J Mol Endocrinol. 1999;22(2):141-50.
Jones JI, Gockerman A, Busby Jr WH, Wright G, Clemmons DR. Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence. Proc Natl Acad Sci U S A. 1993;90(22):10553-7.
Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23(6):824-54.
Duan C, Xu Q. Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions. Gen Comp Endocrinol. 2005;142(1-2):44-52.
Yau SW, Azar WJ, Sabin MA, Werther GA, Russo VC. IGFBP-2-taking the lead in growth, metabolism and cancer. J Cell Commun Signal. 2015;9(2):125-42.
Baxter RC, Binoux M, Clemmons DR, Conover C, Drop SL, Holly JM, et al. Recommendations for nomenclature of the insulin-like growth factor binding protein (IGFBP) superfamily. Growth Horm IGF Res. 1998;8(3):273-4.
Kim HS, Nagalla SR, Oh Y, Wilson E, Roberts Jr CT, Rosenfeld RG. Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc Natl Acad Sci U S A. 1997;94(24):12981-6.
Shimasaki S, Ling N. Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1,-2,-3,-4,-5 and-6). Prog Growth Factor Res. 1991;3(4):243-66.
Pickard A, McCance DJ. IGF-Binding Protein 2-Oncogene or Tumor Suppressor? Front Endocrinol. 2015;6:25.
Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. General considerations for lung function testing. Eur Respir J. 2005;26(1):153-61.
Besnard V, Corroyer S, Trugnan G, Chadelat K, Nabeyrat E, Cazals V, et al. Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and IGFBP-3 expression in oxidant exposed lung epithelial cells. Biochim Biophys Acta. 2001;1538(1):47-58.
Miell JP, Taylor AM, Jones J, Holly JM, Gaillard RC, Pralong FP, et al. The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers. J Endocrinol. 1993;136(3):525-33.
Furuhashi K, Suda T, Nakamura Y, Inui N, Hashimoto D, Miwa S, et al. Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med. 2010;104(8):1204-10.
Korthagen NM, van Moorsel CH, Barlo NP, Ruven HJ, Kruit A, Heron M, et al. Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis. Respir Med. 2011;105(1):106-13.
Hung CF, Rohani MG, Lee SS, Chen P, Schnapp LM. Role of IGF-1 pathway in lung fibroblast activation. Respir Res. 2013;14:102.
Bagnato G, Harari S. Cellular interactions in the pathogenesis of interstitial lung diseases. Eur Respir Rev. 2015;24(135):102-14.
Russo VC, Azar WJ, Yau SW, Sabin MA, Werther GA. IGFBP-2: The dark horse in metabolism and cancer. Cytokine Growth Factor Rev. 2014;26(3):329-46.
Kelley KM, Oh Y, Gargosky SE, Gucev Z, Matsumoto T, Hwa V, et al. Insulinlike growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol. 1996;28(6):619-37.
Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16(1):3-34.
Reeve JG, Morgan J, Schwander J, Bleehen NM. Role for membrane and secreted insulin-like growth factor-binding protein-2 in the regulation of insulin-like growth factor action in lung tumors. Cancer Res. 1993;53(19):4680-5.
Ahasic AM, Zhai R, Su L, Zhao Y, Aronis KN, Thompson BT, et al. IGF1 and IGFBP3 in acute respiratory distress syndrome. Eur J Endocrinol. 2012;166(1):121-9.
Alhamad EH, Cal JG, Shakoor Z, Almogren A, AlBoukai AA. Cytokine gene polymorphisms and serum cytokine levels in patients with idiopathic pulmonary fibrosis. BMC Med Genet. 2013;14:66.
Khalil N, Greenberg AH. The role of TGF-beta in pulmonary fibrosis. Ciba Found Symp. 1991;157:194-207. discussion-11.