From: Smoking induces sex-specific changes in the small airway proteome
Protein name Entrez symbol (Uniprot ID) | Abundance in current smokers | Relevant literature findings, summary and reference |
---|---|---|
Advanced glycosylation end product-specific receptor, soluble | ↓ | Decoy receptor for RAGE (a pattern recognition receptor of the immunoglobulin super-family) [45, 67] |
RAGE signalling is a key driver of inflammation, oxidative stress and alveolar tissues damage in many pulmonary diseases, including COPD and is inhibited by sRAGE [45, 67] | ||
sRAGE | Circulating sRAGE is decreased in COPD [45] | |
(Q15109) | Decrease in serum sRAGE is reported to occur already within 1 h after smoking, reaches its maximum after 8 h and is not fully restored even after 48 h [45] | |
Testican-2 | ↓ | Forming part of the extracellular matrix |
SPOCK2 | It has been suggested to contribute to lung barrier function providing protection against influenza virus infection by restricting entry of the virus into epithelial cells [68] | |
(Q92563) | ||
It is known to modulate matrix metalloproteinases expression and activation [48] | ||
Follistatin-related protein 3 | ↓ | A secreted glycoprotein structurally and functionally related to follistatin [69] |
FSTL3 | It binds and antagonises actions of members of the transforming growth factor beta (TGFβ) superfamily such as activin A (an important regulator of cigarette smoke-induced inflammation) [47, 69] | |
(O95633) | Follistatin, an activin A inhibitor, has been seen to be decreased in cigarette smoke-exposed human bronchial epithelial cells and administration of follistatin was found to attenuate cigarette smoke-induced airway inflammation in mice [47] | |
Protein S | ↓ | Involved in the inhibition of coagulation, clearance of apoptotic cells and inhibition of inflammation [70] |
PROS1 | In plasma, 30–40% of protein S exists in its free form and the remainder is forming a complex with C4b-binding protein (C4BP), an important regulator of complement activation by the classical pathway [70] | |
(P07225) | Protein S localizes C4BP to apoptotic cells where C4BP can down-regulate complement activation and therefore inhibit inflammation at the surface of apoptotic cells [70] | |
Binding of free protein S to the surface of apoptotic cells also enhances phagocytosis of apoptotic cells by macrophages [71] | ||
Adiponectin | ↓ | Anti-inflammatory adipokine that inhibits proinflammatory cytokines and induces anti-inflammatory cytokines [72] |
ADIPOQ | Studies have shown that subjects with emphysema have increased levels of adiponectin in BAL fluid while current smokers without COPD have reduced levels of adiponectin in BAL fluid [72] | |
(Q15848) | ||
Beta-2-microglobulin | ↓ | Component of the class I major histocompatibility complex (MHC I) |
B2M | Identified as a proaging factor [73] | |
(P61769) | Studies have shown that serum β2M is significantly elevated in patients with COPD and the expression of β2M is significantly higher in lung tissue of emphysema [73] | |
Heat shock protein 90 | ↑ | Functions as a molecular chaperone and contributes to the folding, maintenance of structural integrity and proper regulation of a subset of cytosolic proteins [74] |
HSP90 | Plays an important role in the UPR ("unfolded protein response") [58] | |
(P07900) | The expression of heat shock proteins is increased in the alveolar epithelial cells exposed to cigarette smoke extract [62] | |
(P08238) | ||
Translationally-controlled tumor protein (Fortilin) | ↑ | A pro-survival molecule [61] |
TCTP | Plays an important role in the UPR where it protects cells from the apoptotic cell death [61] | |
(P13693) | ||
Ferritin | ↑ | An iron-storage protein [6] |
(P02794) | Increased levels could indicate iron overload [6] | |
(P02792) | ||
Macrophage mannose receptor 1 | ↓ | A pattern recognition receptor found on M2 macrophages which are considered to have anti-inflammatory, wound-healing properties and are involved in the removal of apoptotic cells [76] |
MRC1, CD206 | Reduced expression of MRC1 has been associated with a reduced removal of apoptotic cells in COPD [63] | |
(P22897) | Lack of MRC1 may also result in upregulation of pro-inflammatory cytokines during endotoxin induced lung inflammation in mice [77] | |
Interleukin-1 receptor-like 1 | ↓ | |
IL1RL1, ST2 | ||
(Q01638) | The membrane-bound ST2 binds IL-33, inducing pro-inflammatory immune responses and cytokine production and subsequently eliciting airway inflammation [64, 65] | |
The soluble form of ST2 functions as a decoy receptor neutralizing IL-33 activity and is therefore considered to have an anti-inflammatory function [64, 65] | ||
Adenylate kinase isoenzyme 1 | ↓ | Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism |
AK1 | ||
(P00568) |