Gene expression profiling of familial and sporadic interstitial pneumonia.
BACKGROUND
Idiopathic interstitial pneumonia (IIP) and its familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown.


OBJECTIVE
To evaluate gene expression in the lung tissue of patients with usual interstitial pneumonia or nonspecific interstitial pneumonia that was either familial or nonfamilial in origin, and to compare it with gene expression in normal lung parenchyma.


METHODS
We profiled RNA from the lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal control subjects on a whole human genome oligonucleotide microarray.


RESULTS
Significant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was confirmed in the murine bleomycin model of lung injury, with C57BL/6(CXCR4+/-) mice demonstrating significantly less collagen deposition than C57BL/6(CXCR4+/+) mice. Whereas substantial differences exist between familial and sporadic IIPs, we identified only minor gene expression changes between usual interstitial pneumonia and nonspecific interstitial pneumonia.


CONCLUSIONS
Taken together, our findings indicate that differences in gene expression profiles between familial and sporadic IIPs may provide clues to the etiology and pathogenesis of IIP.
Yang
Ivana V
IV
Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, P.O. Box 12233, MD B3-08, Research Triangle Park, NC 27909, USA. yangi@niehs.nih.gov
Burch
Lauranell H
LH
Steele
Mark P
MP
Savov
Jordan D
JD
Hollingsworth
John W
JW
McElvania-Tekippe
Erin
E
Berman
Katherine G
KG
Speer
Marcy C
MC
Sporn
Thomas A
TA
Brown
Kevin K
KK
Schwarz
Marvin I
MI
Schwartz
David A
DA
D000328:Adult; D000368:Aged; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics
C515255:CXCL12 protein, human; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D051153:Wnt Proteins; D001761:Bleomycin