ILK–PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

Li, Gang; Li, Yeyang; Sun, Jingbo; Lin, Weihua; Zhou, Rixing

doi:10.1038/labinvest.2016.48

Cited by 58 publications

(43 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A,B). The activation of extracellular signal‐regulated kinase (ERK) and phosphoinositide‐3 kinase/protein kinase B (PI3K/AKT) through phosphorylation is well known to regulate cell migration, collagen gel contraction, and skin wound healing (Liu et al, ; Chen et al, ; Li et al, ). The activation of these signaling pathways was suggested in the phenotype conversion of fibroblasts toward myofibroblasts, such as an increased expression of α‐SMA (Mulero‐Navarro et al, ).…”

Section: Discussionmentioning

confidence: 99%

Neuronal PAS Domain 2 (Npas2)‐Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction

Sasaki

Wang

Morinaga

et al. 2019

The Anatomical Record

View full text Add to dashboard Cite

The circadian clock, which consists of endogenous self-sustained and cellautonomous oscillations in mammalian cells, is known to regulate a wide range of peripheral tissues. The unique upregulation of a clock gene, neuronal PAS domain protein 2 (Npas2), observed along with fibroblast aging prompted us to investigate the role of Npas2 in the homeostasis of dermal structure using in vivo and in vitro wound healing models. Time-course healing of a fullthickness skin punched wound exhibited significantly faster wound closure in Npas2−/− mice than wild-type (WT) C57Bl/6J mice. Dorsal skin fibroblasts isolated from WT, Npas2+/−, and Npas2−/− mice exhibited consistent profiles of core clock gene expression except for Npas2 and Per2. In vitro behavioral characterizations of dermal fibroblasts revealed that Npas2−/− mutation was associated with increased proliferation, migration, and cell contraction measured by floating collagen gel contraction and single-cell force contraction assays. Npas2 knockout fibroblasts carrying sustained the high expression level of type XII and XIV FAICT collagens and synthesized dermis-like thick collagen fibers in vitro. Confocal laser scanning microscopy demonstrated the reconstruction of dermis-like collagen architecture in the wound healing area of Npas2−/− mice. This study indicates that the induced Npas2 expression in fibroblasts may interfere with skin homeostasis, wound healing, and dermal tissue reconstruction, providing a basis for novel therapeutic target and strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuronal PAS Domain 2 (Npas2)‐Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction

Sasaki

Wang

Morinaga

et al. 2019

The Anatomical Record

View full text Add to dashboard Cite

show abstract

“…Under normal conditions, ILK signaling is involved in nerve growth factor-stimulated neurite outgrowth and as it was recently reported, in wound repair by regulating fibroblast migration and its differentiation to myofibroblasts [32,33]. …”

Section: Introductionmentioning

confidence: 99%

Integrins in the Spotlight of Cancer

Bianconi

Unseld

Prager

2016

IJMS

127

107

View full text Add to dashboard Cite

Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the Hallmarks of Cancer. In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment.

show abstract

“…Lung local fibroblasts have been shown to transform under the influence of cytokines, such as transforming growth factor-β1 (TGF-β1), into myofibroblasts with the ability to overrepresent and to secrete excessive ECM [5, 6]. Although much is known about the mechanistic aspects of fibroblast differentiation into myofibroblasts, the underlying mechanisms remain unclear [7, 8]. …”

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation analysis in lung fibroblasts co-cultured with silica-exposed alveolar macrophages

Yao

Zhang

et al. 2017

Respir Res

View full text Add to dashboard Cite

BackgroundExposure to crystalline silica is considered to increase the risk of lung fibrosis. The primary effector cell, the myofibroblast, plays an important role in the deposition of extracellular matrix (ECM). DNA methylation change is considered to have a potential effect on myofibroblast differentiation. Therefore, the present study was designed to investigate the genome-wide DNA methylation profiles of lung fibroblasts co-cultured with alveolar macrophages exposed to crystalline silica in vitro.MethodsAM/fibroblast co-culture system was established. CCK8 was used to assess the toxicity of AMs. mRNA and protein expression of collagen I, α-SMA, MAPK9 and TGF-β1 of fibroblasts after AMs exposed to 100 μg /ml SiO2 for 0–, 24–, or 48 h were determined by means of quantitative real-time PCR, immunoblotting and immunohistochemistry. Genomic DNA of fibroblasts was isolated using MeDIP-Seq to sequence. R software, GO, KEGG and Cytoscape were used to analyze the data.ResultsSiO2 exposure increased the expression of collagen I and α-SMA in fibroblasts in co-culture system. Analysis of fibroblast methylome identified extensive methylation changes involved in several signaling pathways, such as the MAPK signaling pathway and metabolic pathways. Several candidates, including Tgfb1 and Mapk9, are hubs who can connect the gene clusters. MAPK9 mRNA expression was significantly higher in fibroblast exposed to SiO2 in co-culture system for 48 h. MAPK9 protein expression was increased at both 24-h and 48-h treatment groups. TGF-β1 mRNA expression of fibroblast has a time-dependent manner, but we didn’t observe the TGF-β1 protein expression.Conclusion Tgfb1 and Mapk9 are helpful to explore the mechanism of myofibroblast differentiation. The genome-wide DNA methylation profiles of fibroblasts in this experimental silicosis model will be useful for future studies on epigenetic gene regulation during myofibroblast differentiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0576-z) contains supplementary material, which is available to authorized users.

show abstract

ILK–PI3K/AKT pathway participates in cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblast

Cited by 58 publications

References 53 publications

Neuronal PAS Domain 2 (Npas2)‐Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction

Neuronal PAS Domain 2 (Npas2)‐Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction

Integrins in the Spotlight of Cancer

Genome-wide DNA methylation analysis in lung fibroblasts co-cultured with silica-exposed alveolar macrophages

Contact Info

Product

Resources

About