Table 2.

Evidence for Sonic Hedgehog Signaling in Human Lung Disease

Disease	Method	Findings	Citation
Parenchymal lung diseases
IPF	Microarray	PTCH1 gene expression altered in IPF lungs	138
	ISH	SHH highly expressed in epithelium of fibrotic areas	139, 142
	qRT-PCR	SHH, PTCH1, and GLI1 up-regulated in IPF lungs	82
	IHC	SHH expressed in hyperplastic alveolar type II cells in fibrotic areas	140, 141
	IHC	PTCH1, SMO, and GLI1 expressed in fibroblastic foci of IPF lungs	82
	ELISA	SHH elevated in BALF from IPF lungs	142
NSIP	ISH	SHH weakly expressed in epithelium, but higher than in normal lung	139
	IHC	SHH expressed in epithelial cells of thickened alveolar walls	140, 141
COP	IHC	SHH expressed in buds of organizing exudate	141
Airway diseases
COPD	GWAS	SNPs in region close HHIP gene on 4q31 linked to decreased lung function (FEV1/FVC ratio) and COPD-related phenotypes	152, 153
	qRT-PCR	HHIP decreased in COPD lungs	153
	WB	HHIP decreased in COPD lungs	153
Asthma	GWAS	SNPs in regions of HHIP on 4q31 and the PTCH1 gene on 9q22-31 linked to decreased lung function (FEV1/FVC ratio) and asthma-related phenotypes	154

Definition of abbreviations: BALF, bronchoalveolar lavage fluid; COP, cryptogenic organizing pneumonia; COPD, chronic obstructive pulmonary disease; GWAS, gene-wide association study; IHC, immunohistochemistry; IPF, idiopathic pulmonary fibrosis; ISH, in situ hybridization; NSIP, nonspecific interstitial pneumonia; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SNP, single-nucleotide polymorphism; WB, Western blot.