Table 6 Top novel targets and its association with asthma.
From: In-silico identification and prioritization of therapeutic targets of asthma
Target | Role in asthma |
|---|---|
POSTN | Periostin is associated with pathogenesis of asthma-associated inflammation in asthma91. Periostin is elevated and found to be a biomarker of type 2 inflammation92. POSTN expression upregulated by IL13 and IL4 cells which has been reduced by treatment with anti–IL-13 (lebrikizumab, tralokinumab) Serum Periostin could be utilized as biomarker for the airway wall thickness in Asthma93 |
COL18A1 | COL18A1 encodes the alpha chain of type XVIII collagen and is the most abundant airway extracellular matrix component, primary determinant of mechanical airway properties94. Epigenetic association studies have shown COL18A1 is associated with lung function development through DNA methylation95 |
JUND | Most of the inflammatory and immune genes contain binding sites for activator protein (AP-1) which is an array of dimeric basic region-leucine zipper proteins of Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) subfamilies96. Recent animal studies indicate that the anti–c-Jun, anti-JunD, and anti–c-Fos antibodies were all able to partly remove the AP-1 complexes and this AP-1 inhibition in the airways may have therapeutic value in the control of established asthma97 |
CCR7 | CC chemokine receptor 7 (CCR7) is directly involved in the pathogenesis of DC‑ and T cell‑mediated allergic asthma98. It plays an important role in the development of ASM hyperplasia in asthma. CCR7 CD4 cells of patients showed significant clinical implications in atopic asthma99 |
ADIPOQ | ADIPOQ gene responsible for expression and secretion of adiponectin which is also associated with the obesity-associated asthma phenotypes100. It is an anti-inflammatory adipokine that increases insulin sensitivity and has cardiovascular protection actions. It is a modulator of the innate and acquired immunity response in asthma101 |
PTEN | Phosphatase and tensin homologue (PTEN) block the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. There were supportive interactions of PI3K-Akt-mTOR and STAT3-miR21-PTEN which controls IgE induced airway remodeling in allergic asthma102. In animal studies there is remarkable reduction in bronchial inflammation and airway hyperresponsiveness observed by intratracheal administration AdPTEN. The above findings indicate a pivotal role of PTEN in asthma103 |
CRP | The high C reactive protein concentration and the age has been found to be associated with the risk of asthma development104. The raised levels of high sensitivity CRP are significantly associated with respiratory state of asthma exacerbation and allergic inflammation105 |
IL17RB | IL17RB is a cognate receptor of IL25 and activation of IL-17RB amplifies allergic-type inflammatory responses by promoting Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK), and nuclear factor-kappaB106. IL-17RB + granulocytes from peripheral blood were increased in subjects with asthma107 |
ADAR | Adenosine is a potent bronchoconstrictor with either pro- or anti-inflammatory effects depending on receptor interactions108. ADAR1 expression levels and protein activity could promote the progression of Asthma. Genetic polymorphisms of adenosine receptors A(1) and A(2A)have been found to be associated with aspirin-intolerant asthma109 |
TGM2 | Transglutaminase 2 (TGM2)TGM2, a novel mediator of asthma pathogenesis, is overexpressed in asthmatic airways44. TGM2 was involved in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression43 |
