Identification of Common Genes and Pathways in Eight Fibrosis Diseases

Abstract

Acute and chronic inflammation often leads to fibrosis, which is also the common and final pathological outcome of chronic inflammatory diseases. To explore the common genes and pathogenic pathways among different fibrotic diseases, we collected all the reported genes of the eight fibrotic diseases: eye fibrosis, heart fibrosis, hepatic fibrosis, intestinal fibrosis, lung fibrosis, pancreas fibrosis, renal fibrosis, and skin fibrosis. We calculated the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment scores of all fibrotic disease genes. Each gene was encoded using KEGG and GO enrichment scores, which reflected how much a gene can affect this function. For each fibrotic disease, by comparing the KEGG and GO enrichment scores between reported disease genes and other genes using the Monte Carlo feature selection (MCFS) method, the key KEGG and GO features were identified. We compared the gene overlaps among eight fibrotic diseases and connective tissue growth factor (CTGF) was finally identified as the common key molecule. The key KEGG and GO features of the eight fibrotic diseases were all screened by MCFS method. Moreover, we interestingly found overlaps of pathways between renal fibrosis and skin fibrosis, such as GO:1901890-positive regulation of cell junction assembly, as well as common regulatory genes, such as CTGF, which is the key molecule regulating fibrogenesis. We hope to offer a new insight into the cellular and molecular mechanisms underlying fibrosis and therefore help leading to the development of new drugs, which specifically delay or even improve the symptoms of fibrosis.

Keywords: CTGF; Monte Carlo feature selection; fibrotic diseases; genes; pathways.

FIGURE 1

The number of overlapped genes among the eight fibrotic diseases. A circular plot illustrating all possible intersections and the corresponding statistics. The eight circles from inside to outside represent the eight fibrotic diseases (1, eye fibrosis; 2, heart fibrosis; 3, hepatic fibrosis; 4, intestinal fibrosis; 5, lung fibrosis; 6, pancreas fibrosis; 7, renal fibrosis; and 8, skin fibrosis), respectively. The height of the bars in the outer layer is proportional to the intersection sizes, as indicated by the numbers on the top of the bars. The color intensity of the bars represents the P-value significance of the intersections.

FIGURE 2

The cross-talk network between renal fibrosis and skin fibrosis. The genes in red refer to the overlaps between renal fibrosis and skin fibrosis, whereas the specific genes in renal fibrosis, skin fibrosis, and GO:1901890 are shown in light yellow, light blue, and pink circles, respectively. The overlapped genes between renal fibrosis and skin fibrosis included CCL2, SIRT1, KLF5, PPARG, AKT1, SHH, NOTCH, SMAD7, TGFB1, CTNNB1, MMP2, CTGF, FN1, ITGB1, PLAUR, MMP14, NOX4, and COL1A1.