Increased mRNA expression of collagen V gene in pulmonary fibrosis of systemic sclerosis.
BACKGROUND
Collagen V shows promise as an inducer of interstitial lung fibrosis in experimental systemic sclerosis (SSc).


METHODS
Remodelling of the pulmonary interstitium was evaluated based on the clinical data and open lung biopsies from 15 patients with SSc. Normal lung tissues obtained from eight individuals who died of traumatic injuries were used as control group. Immunofluorescence, immunohistochemistry, morphometry, tri-dimensional reconstruction and a real-time polymerase chain reaction were used to evaluate the quantity, structure and molecular chains of collagen V. The impact of these markers was tested on clinical data.


RESULTS
The main difference in collagen V content between SSc patients and the control group was an increased, abnormal and distorted fibre deposition in the alveolar septa and the pre-acinar artery wall. The lungs from SSc patients presented [alpha1(V)] and [alpha2(V)] mRNA chain expression increased, but [alpha2(V)] was proportionally increased compared with the control group. High levels of collagen V were inversely associated with vital capacity (r = -0.72; P = 0.002), forced vital capacity (r = -0.76; P < 0.001), forced expiratory volume in 1-s (r = -0.89; P < 0.001) and diffusing capacity for carbon monoxide (r = -0.62; P = 0.04).


CONCLUSIONS
Abnormal collagen V fibres are overproduced in lungs from SSc patients and may play an important role in the pathogenesis of the disease as this molecule regulates tissue collagen assembly. The aberrant histoarchitecture observed in SSc can be related to the overexpression of the [alpha2(V)] gene of unknown origin.
Parra
E R
ER
Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. erparra20003@yahoo.com.br
Teodoro
W R
WR
de Morais
J
J
Katayama
M L H
ML
de Souza
R
R
Yoshinari
N H
NH
Capelozzi
V L
VL
D000328:Adult; D001706:Biopsy; D003094:Collagen / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D015200:Fluoroimmunoassay; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D003094:Collagen