Gu Chang, Shi Xin, Dang Xuening, Chen Jiafei, Chen Chunji, Chen Yumei, Pan Xufeng, Huang Tao
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Front Genet. 2021 Jan 15;11:627396. doi: 10.3389/fgene.2020.627396. eCollection 2020.
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.
急性和慢性炎症常导致纤维化，这也是慢性炎症性疾病常见的最终病理结局。为了探索不同纤维化疾病之间的共同基因和致病途径，我们收集了八种纤维化疾病的所有已报道基因：眼部纤维化、心脏纤维化、肝纤维化、肠道纤维化、肺纤维化、胰腺纤维化、肾纤维化和皮肤纤维化。我们计算了所有纤维化疾病基因的京都基因与基因组百科全书（KEGG）和基因本体论（GO）富集分数。每个基因都使用KEGG和GO富集分数进行编码，这些分数反映了一个基因对该功能的影响程度。对于每种纤维化疾病，通过使用蒙特卡罗特征选择（MCFS）方法比较已报道的疾病基因与其他基因之间的KEGG和GO富集分数，确定了关键的KEGG和GO特征。我们比较了八种纤维化疾病之间的基因重叠情况，最终确定结缔组织生长因子（CTGF）为共同的关键分子。八种纤维化疾病的关键KEGG和GO特征均通过MCFS方法筛选得出。此外，我们有趣地发现肾纤维化和皮肤纤维化之间存在途径重叠，如GO:1901890——细胞连接组装的阳性调控，以及共同的调控基因，如CTGF，它是调节纤维生成的关键分子。我们希望能为纤维化潜在的细胞和分子机制提供新的见解，从而有助于开发新的药物，这些药物能够特异性地延缓甚至改善纤维化症状。
