Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma
Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma
Background/aim: Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has beenreported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on ableomycin (BLM)-induced experimental scleroderma model.Materials and methods: Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 µg) was injected for 3weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 µg/kg per day) was injected subcutaneously for the first3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at theend of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week.Results: Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at boththe third and sixth weeks. Moreover, mRNA expressions of TGF-β1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLMinjected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic andtherapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness.Conclusion: Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I playspathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.
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- Varga J, Abraham D. Systemic sclerosis: a prototypic
multisystem fibrotic disorder. J Clin Invest 2007; 117: 557-567.
- Denton CP, Black CM, Abraham DJ. Mechanisms and
consequences of fibrosis in systemic sclerosis. Nat Clin Pract
Rheumatol 2006; 2: 134-144.
- Krieg T, Abraham D, Lafyatis R. Fibrosis in connective tissue
disease: the role of the myofibroblast and fibroblast-epithelial
cell interactions. Arthritis Res Ther 2007; 9: S4.
- Postlethwaite AE, Shigemitsu H, Kanangat S. Cellular origins of
fibroblasts: possible implications for organ fibrosis in systemic
sclerosis. Curr Opin Rheumatol 2004; 16: 733-738.
- Koca SS, Ozgen M, Dagli F, Tuzcu M, Ozercan IH, Sahin
K, Isik A. Proteasome inhibition prevents development of
experimental dermal fibrosis. Inflammation 2012; 35: 810-817.
- Veraldi KL, Feghali-Bostwick CA. Insulin-like growth factor
binding proteins-3 and -5: central mediators of fibrosis and
promising new therapeutic targets. Open Rheumatol J 2012; 6:
140-145.
- Jones JI, Clemmons DR. Insulin-like growth factors and their
binding proteins: biological actions. Endocr Rev 1995; 16:
3-34.
- Rothe MJ, Altman RD, Falanga V. Plasma somatomedin-C
levels in systemic sclerosis. Br J Dermatol 1988; 119: 639-642.
- Harrison NK, Cambrey AD, Myers AR, Southcott AM, Black
CM, du Bois RM, Laurent GJ, McAnulty RJ. Insulin-like growth
factor-I is partially responsible for fibroblast proliferation
induced by bronchoalveolar lavage fluid from patients with
systemic sclerosis. Clin Sci (Lond) 1994; 86: 141-148.
- Fawzi MM, Tawfik SO, Eissa AM, El-Komy MH, Abdel-Halim
MR, Shaker OG. Expression of insulin-like growth factor-I in
lesional and non-lesional skin of patients with morphoea. Br J
Dermatol 2008; 159: 86-90.
- Feghali CA, Wright TM. Identification of multiple, differentially
expressed messenger RNAs in dermal fibroblasts from patients
with systemic sclerosis. Arthritis Rheum 1999; 42: 1451-1457.
- Knauer AV, Medsger TA. Wright TM, Feghali CA. Insulin-like
growth factor binding proteins contribute to the increased
extracellular matrix production by fibroblasts from patients
with systemic sclerosis (SSc). Arthritis Rheum 2001; 44: 378.
- Krein PM, Winston BW. Roles for insulin-like growth factor I
and transforming growth factor-beta in fibrotic lung disease.
Chest 2002; 122: 289-293.
- Pilewski JM, Liu L, Henry AC, Knauer AV, Feghali-Bostwick
CA. Insulin-like growth factor binding proteins 3 and 5 are
overexpressed in idiopathic pulmonary fibrosis and contribute
to extracellular matrix deposition. Am J Pathol 2005; 166: 399-
407.
- Yasuoka H, Zhou Z, Pilewski JM, Oury TD, Choi AM, FeghaliBostwick CA. Insulin-like growth factor-binding protein-5
induces pulmonary fibrosis and triggers mononuclear cellular
infiltration. Am J Pathol 2006; 169: 1633-1642.
- Lebtahi R, Moreau S, Marchand-Adam S, Debray MP, Brauner
M, Soler P, Marchal J, Raguin O, Gruaz-Guyon A, Reubi JC
et al. Increased uptake of 111In- octreotide in idiopathic
pulmonary fibrosis. J Nucl Med 2006; 47: 1281-1287.
- Borie R, Fabre A, Prost F, Marchal-Somme J, Lebtahi R,
Marchand-Adam S, Aubier M, Soler P, Crestani B. Activation
of somatostatin receptors attenuates pulmonary fibrosis.
Thorax 2008; 63: 251-258.
- Tug T, Kara H, Karaoglu A, Karatas F, Turgut NH, Ayan
E, Boran C, Tug E. The effect of octreotide, an analog of
somatostatin, on bleomycin-induced interstitial pulmonary
fibrosis in rats. Drug Chem Toxicol 2013; 36: 181-186.
- Crestani B, Chapron J, Wallaert B, Bergot E, Delaval P, IsraelBiet D, Lacronique J, Monnet I, Reynaud-Gaubert M, Tazi A
et al. Octreotide treatment of idiopathic pulmonary fibrosis: a
proof-of-concept study. Eur Respir J 2012; 39: 772-775.
- Yamamoto T. Animal model of sclerotic skin induced by
bleomycin: a clue to the pathogenesis of and therapy for
scleroderma. Clin Immunol 2002; 102: 209-216.
- Jia WD, Xu GL, Wang W, Wang ZH, Li JS, Ma JL, Ren WH,
Ge YS, Yu JH, Liu WB. A somatostatin analogue, octreotide,
inhibits the occurrence of second primary tumors and lung
metastasis after resection of hepatocellular carcinoma in mice.
Tohoku J Exp Med 2009; 218: 155-160.
- Jogie-Brahim S, Feldman D, Oh Y. Unraveling insulin-like
growth factor binding protein-3 actions in human disease.
Endocr Rev 2009; 30: 417-437.
- Aston C, Jagirdar J, Lee TC. Enhanced insulin-like growth
factor molecules in idiopathic pulmonary fibrosis. Am J Respir
Crit Care Med 1995; 151: 1597-1603.
- Yasuoka H, Larregina AT, Yamaguchi Y, Feghali-Bostwick
CA. Human skin culture as an ex vivo model for assessing the
fibrotic effects of insulin-like growth factor binding proteins.
Open Rheumatol J 2008; 2: 17-22.
- Thiebaud D, Ng KW, Findlay DM, Harker M, Martin TJ. Insulinlike growth factor I regulates mRNA levels of osteonectin and
pro-alpha-I (i)-collagen in clonal proosteoblastic calvarial
cells. J Bone Miner Res 1990; 5: 761-767.
- Barreca A, De Luca M, Del Monte P, Bondanza S, Damonte
G, Cariola G, Di Marco E, Giordano G, Cancedda R, Minuto
F. In vitro paracrine regulation of human keratinocyte growth
by fibroblast-derived insulin like growth factors. J Cell Physiol
1992; 151: 262-268.
- Shinohara M, Hamasaki Y, Katayama I. Refractory pretibial
myxoedema with response to intralesional insulin-like growth
factor I antagonist (octreotide): down regulation of hyaluronic
acid production by the lesional fibroblasts. Br J Dermatol 2000;
143: 1083-1086.
- Pavlovic M, Saiag P, Lotz JP, Marinho E, Clerici T, Izrael V.
Regression of sclerodermatous skin lesions in a patient with
carcinoid syndrome treated by octreotide. Arch Dermatol
1995; 131: 1207-1208.