Table 1.
Summary of relevant idiopathic pulmonary fibrosis (IPF) genes identified by transcriptome profiling.
| Gene IDa | Gene name | Direction of expression | Tissue localization | Relevant pathway | Reference |
|---|---|---|---|---|---|
| Expressed in lung epithelium in IPF | |||||
| MMP7 | Matrix metallopeptidase 7 | Increased | Lung (alveolar epithelial cells and fibroblasts), peripheral blood and BAL | Extracellular matrix degradation, defensins, SPP1, and WNT/β-catenin pathway | (4, 5, 21–27) |
| MMP3 | Matrix metallopeptidase 3 | Increased | Lung, epithelial cells | Extracellular matrix degradation, β-catenin pathway | (28) |
| MMP19 | Matrix metallopeptidase 19 | Increased | Lung, epithelial cells | Extracellular matrix degradation, PTGS2 pathway | (29) |
| MMP1 | Matrix metallopeptidase 1 | Increased | Lung, epithelial cells | Extracellular matrix degradation, mitochondrial function/HIF-1-alpha pathway | (30) |
| SPP1 | Osteopontin | Increased | Lung (epithelial cells) | Extracellular matrix degradation | (9, 22) |
| IGFBP-4 | Insulin-like growth factor binding protein 4 | Increased | Lung (alveolar and basal cells) | IGF1 pathway | (5, 24) |
| CCNA2 | Cyclin A2 | Increased | Lung (alveolar epithelial cells) | Cell cycle regulation | (10) |
| HIF1A | Hypoxia-inducible factor-1 alpha | Increased | Lung (alveolar epithelial cells) | Hypoxia, p53/VEGF pathways | (31) |
| CAV1 | Caveolin-1 | Decreased | Lung | Cell cycle regulation, TGF-b/JNK pathway | (6) |
| SYN-2 | Syndecan-2 | Increased | Lung, alveolar macrophages | TGF-b pathway | (32) |
| TAGLN | Transgelin | Increased | Lung, ATII cells | TGF-b pathway | (33) |
| CRLF 1 | Cytokine receptor-like factor 1 | Increased | Lung, ATII | Th1 cells inflammatory response | (34) |
| EGFR | Epidermal growth factor receptor | Increased | Lung, epithelial cells | Reepithelization | (35) |
| LYCAT | Lysocardiolipin acyltransferase | Decreased | Lung (epithelial cells), peripheral blood mononuclear cell (PBMC) | Mitochondrial membrane potential | (36) |
| SERPINF1 (PEDF) | Pigment epithelium-derived factor | Increased | Lung | Angiogenesis | (37) |
| Fibroblasts related gene expression in IPF | |||||
| FOXF1 | Forkhead box F1 | Increased | Lung | COL1/ARPC1 pathway | (38) |
| VCAM-1 | Vascular cell adhesion molecule 1 | Increased | Lung, fibroblast foci and blood vessels | TGF-b/ERK/Cyclin D pathway | (39) |
| FKBP10 | FK506-binding protein 10 | Increased | Lung, fibroblasts, and CD68 (+) macrophages | TGF-b/Col I synthesis | (40) |
| RXFP1 | Relaxin/insulin-like family peptide receptor 1 | Decreased | Lung | TGF-b | (41) |
| TAZ | Transcriptional coactivator with PDZ-binding motif | Increased | Lung | CTGF and Col1 pathways | (42) |
| IGFBP3, IGFBP5 | Insulin-like growth factor binding proteins 3 and 5 | Increased | Lung | IGF pathway | (43) |
| WNT pathway in IPF | |||||
| WNT1, 3a, 5a, 7b, 10b, Fzd2 and 3, β-catenin, Lef1, Gsk-3β | Wingless and others | Increased | Lung, fibroblasts, alveolar and bronchial epithelium | Wnt signaling | (23, 44, 45) |
| LRP5 | Wnt co-receptor | Increased | Lung, PBMC | Wnt and TGF-b pathway | (46) |
| WISP1 | Wnt1-inducible signaling protein-1 | Increased | Lung | Wnt signaling | (47) |
| Apoptotic response in IPF | |||||
| TWIST1 | Twist basic helix–loop–helix transcription factor 1 | Increased | Lung—fibroblastic foci | Apoptosis/PDGF pathway | (48) |
| CXCL12 | Chemokine ligand 12 | Increased | Lung | Inflammation | (8) |
| TNSF10, BAX, CASP6 | Apoptotic regulators | Altered expression | Lung | Apoptosis | (49) |
| SHP2 (PTPN11) | SH2 domain-containing tyrosine phosphatase-2 | Decreased | Lung | Apoptosis/Tyr and Ser/Thr kinase pathways | (50) |
| Host defense implicated in IPF | |||||
| DEFA3–4 | Defensin alpha 3 and 4 | Increased | Lung and peripheral blood | Host defense | (10, 51) |
| AGER (RAGE) | Advanced glycosylation end product-specific receptor | Decreased | Lung and peripheral blood | Inflammation | (24, 52) |
| Mitochondria-related genes in IPF | |||||
| PINK1 | PTEN-induced putative kinase 1 | Decreased | Lung | Dysfunction of mitochondria | (53) |
| DIO2 | Iodothyronine deiodinase 2 | Increased | Lung | TH pathway/mitochondrial biogenesis | (54) |