GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease

Abstract

Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.

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“…Additionally, MMP9 is a crucial regulator implicated in ESCC outcome and prognosis [41], and its expression can be regulated by GLI2 in melanoma cells [42]. A previous document proved that GPNMB can influence MMP9 expression in chronic obstructive pulmonary disease [43]. Our data also showed that Tan can downregulate MMP9 expression by diminishing GPNMB level in ESCC cells.…”

Gut Microbiome and Transcriptomic Changes in Cigarette Smoke-Exposed Mice Compared to COPD and CD Patient Datasets

“…MMP-12 belongs to the matrix metalloproteinases family, which contributes to the remodeling of the small airways and to the proteolytic degradation of the alveolar wall matrix, leading to emphysema [21]. GPNMB, an endogenous glycoprotein, can influence the pathogenesis of COPD, for instance, through its contribution to tissue remodeling in COPD by promoting the secretion of MMP-9, another matrix metalloproteinase [22]. CTSK is a cysteine protease that is stimulated by inflammatory cytokines and released after tissue injury, contributing to the destruction of connective tissues in the lungs [23].…”

The anti-tumor activity of tangeretin in esophageal squamous cell carcinoma by inhibiting GLI2-mediated transcription of GPNMB

“…Additionally, MMP9 is a crucial regulator implicated in ESCC outcome and prognosis [ 41 ], and its expression can be regulated by GLI2 in melanoma cells [ 42 ]. A previous document proved that GPNMB can influence MMP9 expression in chronic obstructive pulmonary disease [ 43 ]. Our data also showed that Tan can down-regulate MMP9 expression by diminishing GPNMB level in ESCC cells.…”