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Titolo:
Differential mRNA expression of insulin-like growth factor-1 splice variants in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis
Autore:
Bloor, CA; Knight, RA; Kedia, RK; Spiteri, MA; Allen, JT;
Indirizzi:
N Staffordshire Hosp, Directorate Resp Med, Lung Injury & Inflammat Res Grp, Stoke On Trent ST4 6QG, Staffs, England N Staffordshire Hosp Stoke On Trent Staffs England ST4 6QG taffs, England
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
fascicolo: 2, volume: 164, anno: 2001,
pagine: 265 - 272
SICI:
1073-449X(20010715)164:2<265:DMEOIG>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACTOR-I GENE; FACTOR-BINDING PROTEIN-5; IGF-I; ALVEOLAR MACROPHAGES; FACTOR-BETA; HORMONE; CELLS; RECEPTOR; THROMBIN; AGE;
Keywords:
IGF-1; mRNA transcripts; idiopathic pulmonary fibrosis; pulmonary sarcoidosis; fibroblasts; competitive RT-PCR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Bloor, CA N Staffordshire Hosp, Directorate Resp Med, Lung Injury & Inflammat Res Grp, Newcastle Rd, Stoke On Trent ST4 6QG, Staffs, England N Staffordshire Hosp Newcastle Rd Stoke On Trent Staffs England ST4 6QG
Citazione:
C.A. Bloor et al., "Differential mRNA expression of insulin-like growth factor-1 splice variants in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis", AM J R CRIT, 164(2), 2001, pp. 265-272

Abstract

Insulin-like growth factor-1 (IGF-1) is a highly mitogenic polypeptide detectable in human lung. Using competitive reverse transcriptase/polymerase chain reaction (RT-PCR), expression of four IGF-1 transcripts was examined in bronchoalveolar lavage cells (BALC) from normal subjects, idiopathic pulmonary fibrosis (IPF), stage I/II (no fibrosis), and stage III/IV (confirmedfibrosis) pulmonary sarcoidosis patients, and fibroblast strains isolated from normal and IPF lungs. Transcripts studied were Class I and Class 2 (exons 1 or 2, respectively) with IGF-1 Eb or IGF-1 Ea (exons 5 or 6, respectively). Total IGF-1 expression was downregulated in BALC of both patients with IPF (p < 0.01) and patients with sarcoidosis (p < 0.04) compared with healthy subjects. In contrast, both constitutive (p < 0.003) and transforminggrowth factor-P (TGF-P)induced (p < 0.02) IGF-1 expression was higher in fibrotic, compared with normal, fibroblasts. These changes were associated with differential expression of IGF-1 splice variants. Healthy subjects and sarcoidosis patients without fibrosis showed similar expression of Class 1/Class 2 and IGF-1Ea/IGF-1Eb. However, patients with fibrosis demonstrated discordant, increased relative abundance of Class 1 transcripts (p < 0.01). In parallel, all fibrosis patients failed to express Class 2, IGF-1Eb formsand sarcoidosis patients with fibrosis did not express the Class 1, IGF-1Eb variant either. Fibrotic fibroblasts expressed higher constitutive levelsof Class 1, IGF-1Ea transcripts compared with normal fibroblasts. Class 2,IGF-1Eb forms were moderately expressed by fibroblasts only after stimulation with TGF-P, which also further increased levels of Class 1, IGF-1 Ea transcripts. Our findings suggest that transition from a healthy to a fibrotic phenotype occurs in association with a changing pattern of IGF-1 mRNA heterogeneity and leads us to hypothesize a potential role for specific IGF-1 variants in fibrogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 10:58:34