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Gene & Protein in Disease Drugs and immune infiltration in IPF

mouse study demonstrated increased interaction between research has been conducted on the role of TMEM100, a
PDIA3 and SPP1, which is linked to reduced lung function transmembrane protein with diverse biological functions,
in patients with IPF. Elevated blood MMP7 levels have in IPF, warranting further investigation. CPB2, also
22
18
been reported in subclinical familial pulmonary fibrosis, known as plasma carboxypeptidase B, suppressed C5a-
with the expression of MMP7 showing a correlation induced inflammation in autoimmune arthritis models. 23,24
with IPF severity. MMP7 knockout mice showed However, research on CPB2 in IPF is sparse, and
19
reduced bleomycin (BLM)-induced fibrosis, suggesting a considering the involvement of the autoimmune system
profibrotic role of MMP7 in IPF. IL13RA2 is a hallmark and inflammation in IPF pathogenesis, the role of CPB2
20
of IPF but cannot predict acute exacerbation. Limited in IPF warrants further exploration. VIPR1, a G-protein-
21
coupled receptor predominantly expressed in healthy
tissues, is involved in various physiological processes,
including glycogen metabolism and immune system
modulation. VIPR1 is associated with several cancers,
25
with high expression levels in breast, gastric, and colorectal
cancers and low expression levels in lung and liver cancers.
It is associated with cancer migration, invasion, cell
proliferation, and differentiation. 26,27 However, research
on VIPR1 in IPF is limited, making its function worth
exploring.
Further analysis revealed COL15A1 and COL6A3 as
hub genes. COL15A1 encodes the alpha chain of collagen
XV, primarily produced by mesenchymal cells such as
myocytes and adipocytes. It possesses antiangiogenic and
antitumor properties and plays a key role in maintaining
tissue homeostasis in various organs, such as the liver, eye,
Figure 7. Prediction of potential drugs targeting hub genes using kidney, and central nervous system. 28,29 Although research
DrugBank, CTD, and DGIdb. Green squares represent drugs/compounds, suggests a link between COL15A1 and IPF development,
30
and red circles represent genes
Abbreviations: CTD: Comparative Toxicogenomics Database; DGIdb: the mechanisms underlying this link remain poorly
Drug-Gene Interaction Database. understood. In contrast, COL6A3 encodes a component
A B

C D

Figure 8. Macromolecular docking images of potential drugs with COL15A1 and COL6A3. (A) Molecular docking of cyclosporine and COL15A1.
(B) Molecular docking of cyclosporine and COL6A3. (C) Molecular docking of dexamethasone and COL6A3. (D) Molecular docking of (+)-JQ1
compound and COL6A3.
Abbreviations: COL15A1: Collagen type XV alpha 1 chain; COL6A3: Collagen type VI alpha 3 chain.

Volume 3 Issue 4 (2024) 10 doi: 10.36922/gpd.4101