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Updated: Nov 19, 2025
Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
Published on: November 4, 2019
RNA sequencing analysis of FGF2-responsive transcriptome in skin fibroblasts
Baojin Wu1, Xinjie Tang1, Zhaoping Zhou1
1Department of Plastic Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
Background:
Fibroblast growth factor 2 (FGF2) is a highly pleiotropic cytokine with antifibrotic activity in wound healing. During the process of wound healing and fibrosis, fibroblasts are the key players. Although accumulating evidence has suggested the antagonistic effects of FGF2 in the activation process of fibroblasts, the mechanisms by which FGF2 hinders the fibroblast activation remains incompletely understood. This study aimed to identify the key genes and their regulatory networks in skin fibroblasts treated with FGF2.
Methods:
RNA-seq was performed to identify the differentially expressed mRNA (DEGs) and lncRNA between FGF2-treated fibroblasts and control. DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, the networks between mRNAs and lncRNAs were constructed by Pearson correlation analysis and the networkanalyst website. Finally, hub genes were validated by real time-PCR.
Results:
Between FGF2-treated fibroblasts and control fibroblasts, a total of 1475 DEGs was obtained. These DEGs were mainly enriched in functions such as the ECM organization, cell adhesion, and cell migration. They were mainly involved in ECM-receptor interaction, PI3K-Akt signaling, and the Hippo pathway. The hub DEGs included COL3A1, COL4A1, LOX, PDGFA, TGFBI, and ITGA10. Subsequent real-time PCR, as well as bioinformatics analysis, consistently demonstrated that the expression of ITGA10 was significantly upregulated while the other five DEGs (COL3A1, COL4A1, LOX, PDGFA, TGFBI) were downregulated in FGF2-treated fibroblasts. Meanwhile, 213 differentially expressed lncRNAs were identified and three key lncRNAs (HOXA-AS2, H19, and SNHG8) were highlighted in FGF2-treated fibroblasts.
Conclusion:
The current study comprehensively analyzed the FGF2-responsive transcriptional profile and provided candidate mechanisms that may account for FGF2-mediated wound healing.
Insights
Fibroblast growth factor 2 (FGF2) hinders fibroblast activation, a key process in wound healing. This study identified key genes and regulatory networks, revealing FGF2
Area of Science:
- Molecular Biology
- Cell Biology
- Bioinformatics
Background:
- Fibroblast growth factor 2 (FGF2) is a cytokine with antifibrotic activity crucial for wound healing.
- Fibroblast activation is central to wound healing and fibrosis, but FGF2's inhibitory mechanisms are not fully understood.
- This study investigates the molecular mechanisms underlying FGF2's effect on skin fibroblast activation.
Purpose of the Study:
- To identify key genes and regulatory networks in skin fibroblasts treated with FGF2.
- To elucidate the molecular mechanisms by which FGF2 influences fibroblast activation and wound healing.
Main Methods:
- RNA sequencing (RNA-seq) was employed to identify differentially expressed messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) in FGF2-treated fibroblasts.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed genes (DEGs).
- mRNA-lncRNA networks were constructed, and hub genes were validated using real-time quantitative polymerase chain reaction (RT-qPCR).
Main Results:
- A total of 1475 DEGs were identified, enriched in extracellular matrix (ECM) organization, cell adhesion, and migration pathways.
- Key pathways involved include ECM-receptor interaction, PI3K-Akt signaling, and the Hippo pathway.
- Hub genes ITGA10 was upregulated, while COL3A1, COL4A1, LOX, PDGFA, and TGFBI were downregulated. 213 differentially expressed lncRNAs were identified, with HOXA-AS2, H19, and SNHG8 highlighted.
Conclusions:
- This study provides a comprehensive analysis of the FGF2-responsive transcriptional profile in skin fibroblasts.
- Identified genes and pathways offer insights into potential mechanisms of FGF2-mediated antifibrotic effects in wound healing.
- The findings contribute to understanding FGF2's role in regulating fibroblast behavior during tissue repair.
