Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5.
Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5.
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DOI：
10.3390/ijms222212609
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发表时间：
2021-11-22
影响因子：
5.6
通讯作者：
Feghali-Bostwick C
中科院分区：
文献类型：
--
作者：
Nguyen XX;Renaud L;Feghali-Bostwick C
肺纤维化是一种严重的疾病，其特征在于细胞外基质（ECM）成分的过度产生和重塑。胰岛素样生长因子结合蛋白5（IGFBP 5）是IGFBP蛋白家族的保守成员，其在纤维化组织中过表达并促进纤维化。我们使用RNA测序（RNAseq）来鉴定表达人IGFBP 5的纯合（HOMO）转基因小鼠（hIGFBP 5）和野生型小鼠（WT）的原代肺成纤维细胞（pFB）之间的差异表达基因（DEG）。差异表达分析结果显示hIGFBP 5 pFB中有2819个DEG。功能富集分析证实了IGFBP 5的促纤维化特征，并揭示了其对基本信号传导途径的影响，仅举几例，包括精氨酸-细胞因子受体相互作用、粘着斑、AGE-β信号传导、钙信号传导和神经活性配体-受体相互作用。值得注意的是，hIGFBP 5表达pFB中7%的DEG是受体和整联蛋白。此外，hub基因分析揭示了12个hub基因，包括Fpr 1、Bdkrb 2、Mchr 1、Nmur 1、Cnr 2、P2 ry 14和Ptger 3。进行验证测定以补充RNAseq数据。他们证实了培养的pFB中相应蛋白质水平的显着差异。我们的研究通过可能的受体相互作用驱动纤维化和组织重塑，为IGFBP 5相关肺纤维化的分子机制提供了新的见解。
Pulmonary fibrosis is a serious disease characterized by extracellular matrix (ECM) component overproduction and remodeling. Insulin-like growth factor-binding protein 5 (IGFBP5) is a conserved member of the IGFBP family of proteins that is overexpressed in fibrotic tissues and promotes fibrosis. We used RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) between primary lung fibroblasts (pFBs) of homozygous (HOMO) transgenic mice expressing human IGFBP5 (hIGFBP5) and wild type mice (WT). The results of the differential expression analysis showed 2819 DEGs in hIGFBP5 pFBs. Functional enrichment analysis confirmed the pro-fibrotic character of IGFBP5 and revealed its impact on fundamental signaling pathways, including cytokine–cytokine receptor interaction, focal adhesion, AGE-RAGE signaling, calcium signaling, and neuroactive ligand-receptor interactions, to name a few. Noticeably, 7% of the DEGs in hIGFBP5-expressing pFBs are receptors and integrins. Furthermore, hub gene analysis revealed 12 hub genes including Fpr1, Bdkrb2, Mchr1, Nmur1, Cnr2, P2ry14, and Ptger3. Validation assays were performed to complement the RNAseq data. They confirmed significant differences in the levels of the corresponding proteins in cultured pFBs. Our study provides new insights into the molecular mechanism(s) of IGFBP5-associated pulmonary fibrosis through possible receptor interactions that drive fibrosis and tissue remodeling.
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DOI：
10.18632/aging.202406
发表时间：
2021-01-20
期刊：
Aging
影响因子：
--
作者：
Deng G;Li L;Ouyang Y
通讯作者：
Ouyang Y
影响因子：
7
作者：
Ashburner, M;Ball, CA;Yoon, J
通讯作者：
Yoon, J
影响因子：
7.8
作者：
BORNSTEIN, P
通讯作者：
BORNSTEIN, P
影响因子：
3.1
作者：
Estany S;Vicens-Zygmunt V;Llatjós R;Montes A;Penín R;Escobar I;Xaubet A;Santos S;Manresa F;Dorca J;Molina-Molina M
通讯作者：
Molina-Molina M
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG