Research Paper Volume 14, Issue 17 pp 6957—6974

Integrated PPI- and WGCNA-retrieval of hub gene signatures for soft substrates inhibition of human fibroblasts proliferation and differentiation

Ziran Xu1, , Tian Zhou2, , Yin Wang1, , Leijie Zhu3, , Jihao Tu4, , Zhixiang Xu1, , Lisha Li1, , Yulin Li1, ,

  • 1 The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
  • 2 The First Norman Bethune Clinical Medical College, Jilin University, Changchun 130021, China
  • 3 The Third Norman Bethune Clinical Medical College, Jilin University, Changchun 130021, China
  • 4 Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun 130021, China

Received: May 13, 2022       Accepted: August 23, 2022       Published: September 2, 2022
How to Cite

Copyright: © 2022 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Fibroblasts (FBs) are the most important functional cells in the process of wound repair, and their functions can be activated by different signals at the pathological site. Although wound repair is associated with microenvironmental stiffness, the effect of matrix stiffness on FBs remains elusive. In this study, TGF-β1 was used to mimic the fibrotic environment under pathological conditions. We found that the soft substrates made FBs slender compared with tissue culture plastic, and the main altered biological function was the inhibition of proliferation and differentiation ability. Through PPI and WGCNA analysis, 63 hub genes were found, including GADD45A, CDKN3, HIST2H3PS2, ACTB, etc., which may be the main targets of soft substrates affecting the proliferation and differentiation of FBs. Our findings not only provide a more detailed report on the effect of matrix stiffness on the function of human skin FBs, but also may provide new intervention ideas for improving scars and other diseases caused by excessive cell proliferation, with potential clinical application prospects.


FBs: fibroblasts; hFFs: human foreskin fibroblasts; TCP: tissue culture plastic; TGF-β1: transforming growth factor β1; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DEGs: differentially expressed genes; BP: biological process; CC: cellular component; MF: molecular function; GSEA: gene set enrichment analysis; PPI: protein-protein interaction network; WGCNA: weighted gene coexpression network analysis.