Table 4.

Epithelial cell transcriptome—genes for which expression remained in strong positive or negative associations with reticular basement membrane thickness (correlation coefficients ≥ 0.6 or ≤ −0.6).

Gene	Alias for Gene	Correlation Coefficient	Potential Linkage with Airway and Asthma Pathology
MIS12	MIS12 kinetochore complex component	0.745	Plays an essential role in chromosome segregation [9]. The higher expression suggests increased proliferation potency of airway epithelial cells.
CDK20	Cyclin-dependent kinase 20	0.727	The encoded kinase may activate airway epithelial cell growth and proliferation [8].
TACC2	Transforming acidic coiled-coil protein 2	0.608	A centrosome- and microtubule-interacting protein, involved in homologous recombination repair [22], attenuates DNA damage and cytotoxicity in immortalized human bronchial epithelial cells [23].
NEK5	NIMA related kinase 5	0.625	Regulates centrosome integrity and is involved in cell proliferation [24]. The higher expression suggests increased proliferation potency of airway epithelial cells.
ORC5	The origin recognition complex subunit 5	0.603	Promotes DNA replication [25]. The higher expression might indicate increased proliferation potency of airway epithelial cells.
AMBRA1	Autophagy and beclin 1 regulator 1	0.626	Regulates autophagy, cell survival, and proliferation [26]. A positive correlation with reticular basement membrane (RBM) thickness suggests that autophagy mechanisms are likely involved in airway remodeling pathology.
GAD1	Glutamate decarboxylase 1	0.696	An enzyme catalyzing gamma-aminobutyric acid (GABA) production. GABA may be produced by human epithelial cells, likely relaxing airway smooth muscle [27]. Higher expression of GAD1 in airway transcriptome has also been documented in chronic obstructive pulmonary disease (COPD) patients [28].
MYO1B	Myosin I B	0.658	A motor protein related to the actin filament-based cell organization and movement [29]. Higher airway epithelial cell expression might reflect epithelial-to-mesenchymal transition, a structural modification, whereby epithelial cells lose cell–cell polarity and display mesenchymal features, such as migratory properties [5].
CORO2A	Coronin 2A	0.6	An actin-binding protein involved in cell cycle progression, signal transduction, cell motility, apoptosis, and gene expression [30]. Higher expression in airway epithelium may also reflect the epithelial-to-mesenchymal transition.
TPM1	Tropomyosin alpha-1 chain	0.603	An actin-binding protein involved in the contractile cell system [31]. The higher expression may also reflect the epithelial-to-mesenchymal transition.
OTOF	Otoferlin	0.612	A protein involved in the vesicular release. Pathological mutations in OTOF are related to deafness. Although its exact role in asthma pathology is unknown, it may be involved in airway mucus secretion [32].
TPH1	Tryptophan hydrolase 1	0.643	A hydroxylase that catalyzes the first rate-limiting step in the biosynthesis of serotonin [33], an important inflammatory mediator in asthma. Serotonin modulates the function of various inflammatory cells, such as mast cells, eosinophils, dendritic cells, and lung epithelium. Higher levels have been shown in asthma patients’ airways; however, its exact source in the lungs is unknown [34].
RNF34	Ring finger protein 34	0.683	A ring finger containing protein, involved in protein–protein and protein–DNA interactions. It likely protects epithelial cells from premature apoptosis [35].
EEF2	Eukaryotic translation elongation factor 2	0.658	An essential factor in cell protein biosynthesis. The higher expression suggests increased protein translation potency in asthma patients with thicker RBM [36].
STAP1	Signal transducing adaptor family member 1	0.609	Positively regulates gene expression and signal transduction. The exact role in asthma pathology is unknown; however, it is abundant in activated human B cells [37].
OAS2	2′-5′-oligoadenylate synthetase 2	0.703	An interferon-induced antiviral ribonuclease L that destabilizes double-stranded viral RNA. It plays a critical role in the cellular innate antiviral response. A positive correlation with RBM thickness suggests that viral infections, essential asthma exacerbation triggers, might also be involved in airway remodeling pathology. The encoded protein also regulates cell apoptosis, growth, differentiation, and gene expression [20].
USH2A	Usherin	0.601	An extracellular matrix protein, found in many tissues’ basement membrane, including the lungs [18].
LAMA3	Laminin subunit α3	0.615	A protein belonging to the laminin family. Laminins are essential for the formation and function of the basement membrane [17]. Higher airway expression has been linked with COPD and idiopathic pulmonary fibrosis patients [38].
PCDHA3	Protocadherin alpha 3	0.609	A neural cadherin-like cell adhesion protein. Its role in airways is unknown; however, it might be related to the neural network and synaptic organization in airway remodeling pathology [39].
PDS5	Cohesin associated factor B	−0.643	A protein that negatively regulates cell proliferation [10]. The lower expression suggests increased proliferation potency of airway epithelial cells.
HPRT1	Hypoxanthine phosphoribosyltransferase 1	−0.647	A transferase engaged in purine salvage pathway. Its deficiency might be associated with increased local uric acid production [40]. Soluble uric acid is an endogenous danger signal, which may stimulate neovascularization [41] and cell proliferation [42]. Furthermore, hypoxia-inducible factor 1 α (HIF1-α) strongly upregulates HPRT1; therefore, a lower expression of HPRT1 might indicate a worse response to oxidative stress in airway epithelium [40].
RNF13	Ring finger protein 13	−0.636	A ring zinc finger containing protein, promoting cell apoptosis [43]. The lower expression might indicate the anti-apoptotic potency of airway epithelial cells.
MRPL37	Mitochondrial ribosomal protein L37	−0.66	A large subunit of mitochondrial ribosomal proteins, which catalyzes protein production within the mitochondrion. Recent investigations have uncovered this protein’s pro-apoptotic role [44,45]; therefore, its lower expression might indicate anti-apoptotic potency of airway epithelial cells.
CACNA1G	Calcium voltage-gated channel subunit α1 G	−0.615	A transmembrane voltage-dependent calcium channel promoting cell death. The decreased expression suggests lower apoptotic activity [46].
PIEZO2	Piezo type mechanosensitive ion channel component 2	−0.6	A stretch-gated ion channel that senses airway stretches [47]. Lower expression in those with a thicker RBM might indicate a weaker response to epithelial cells’ mechanical stimuli. Lower PIEZO2 expression has been shown in COPD patients [28].
CA3	Carbonic anhydrase 3	−0.606	A carbonic anhydrase that facilitates the reversible hydrating of carbon dioxide. Lower expression in those with thicker RBM might indicate a possible weaker contraction ability or a worse response to oxidative stress in airway epithelium because CA3 is upregulated by HIF1-α [48].
KIF11	Kinesin family member 11	−0.645	A motor cell protein involved i.a. in cilia beating and cell division. The lower expression might suggest impaired cilia function in those with a thicker RBM [49].
C21orf58	Chromosome 21 open reading frame 58	−0.629	Exact biological roles are unknown