Table 1 Description of inflammation- and fibrosis-associated genes investigated in human (OP and control) lungs and in transgenic and nontransgenic mice

Bone morphogenetic protein 4

BMP4

Bmp4

BMPs are a group of growth factors also known as cytokines and are part of the transforming growth factor beta superfamily. BMPs induce cartilage and bone formation

Bone morphogenetic protein receptor, type 1B

BMPR1B

Bmpr1b

On ligand binding, a receptor complex forms consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators

Chemokine (C-C motif) ligand 2

CCL2

Ccl2

This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4

Collagen, type III, alpha 1

COL3A1

Col3a1

Collagen type III occurs in most soft connective tissues (skin, lung, uterus, intestine and the vascular system) along with type I collagen. Involved in the regulation of cortical development

Chemokine (C-X-C motif) ligand 12

CXCL12

Cxcl12

Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. It functions as the ligand for the G protein-coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis

Chemokine (C-X-C motif) receptor 4

CXCR4

Cxcr4

Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels

Interleukin 6

IL6

Il6

Cytokine that functions in inflammation and the maturation of B cells. In addition, it has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor alpha

Matrix metallopeptidase 2

MMP2

Mmp2

Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, it can also act on several non-matrix proteins such as big endothelin-1 and beta-type CGRP promoting vasoconstriction

Protein tyrosine kinase 2

PTK2

Ptk2

Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis

SMAD family member 1

SMAD1

Smad1

This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase, type I. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation

SMAD family member 3

SMAD3

Smad3

Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and is thought to play a role in the regulation of carcinogenesis

Transforming growth factor, beta 1

TGFB1

Tgfb1

Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. At low concentrations in concert with IL-6 and IL-21, it leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells

Thrombospondin 1

THBS1

Thbs1

This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. It can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1 and has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis

Tissue inhibitor of metalloproteinase 1

TIMP1

Timp1

Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on all MMPs, except on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades

Tissue inhibitor of metalloproteinase 2

TIMP2

Timp2

In addition to an inhibitory role against metalloproteinases, this protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodeling of the extracellular matrix