Wound Healing and Epithelial–Mesenchymal Transition in the Lens Epithelium: Roles of Growth Factors and Extracellular Matrix

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.

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The Role of the Extracellular Matrix Components in Cutaneous Wound Healing

BioMed Research International ◽

10.1155/2014/747584 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 113

Author(s):

Pawel Olczyk ◽

Łukasz Mencner ◽

Katarzyna Komosinska-Vassev

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Growth Factors ◽

Wound Repair ◽

Structural Integrity ◽

Healing Process ◽

Cellular Functions ◽

Extracellular Matrix Components ◽

Essential Components ◽

Matrix Components

Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors’ action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed.

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Carvacrol Ameliorates Transforming Growth Factor-β1-Induced Extracellular Matrix Deposition and Reduces Epithelial-Mesenchymal Transition by Regulating The Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway In Hk-2 Cells

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:501-507 ◽

2021 ◽

Vol 19 (4) ◽

pp. 501-507

Author(s):

Yunhe Gu ◽

Peiyao Guo ◽

Guangbiao Xu

Keyword(s):

Extracellular Matrix ◽

Growth Factor ◽

Renal Fibrosis ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Transforming Growth Factor Β1 ◽

Mesenchymal Transition ◽

Matrix Deposition ◽

Extracellular Matrix Deposition ◽

Dose Dependent

Transforming growth factor-β1 promotes excessive extracellular matrix deposition and epithelial-mesenchymal transition of tubular epithelial cells, thus stimulating the progression of renal fibrosis. Carvacrol has been shown to alleviate cardiac and liver fibrosis and attenuate renal injury. However, the role of carvacrol on renal fibrosis has not been examined. First, measurements using Cell Counting Kit-8 showed that carvacrol reduced cell viability of tubular epithelial cell line HK-2 in a dose-dependent fashion. Second, transforming growth factor-β1 induced excessive extracellular matrix deposition in HK-2 cells with enhanced collagen I, collagen IV, and fibronectin expression. However, carvacrol decreased the expression of collagen I, collagen IV in a dose-dependent manner and fibronectin to attenuate the extracellular matrix deposition in HK-2. Third, carvacrol attenuated TGF-β1-induced decrease of E-cadherin and increase of snail, vimentin, and alpha-smooth muscle actin in HK-2 cells. Transforming growth factor-β1-induced increase in PI3K and AKT phosphorylation in HK-2 were also reversed by carvacrol. Collectively, carvacrol ameliorates renal fibrosis through inhibition of transforming growth factor-β1-induced extracellular matrix deposition and epithelial-mesenchymal transition of HK-2 cells, providing potential therapy for the treatment of renal fibrosis.

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Epithelial-Mesenchymal Transition, TGF-β, and Osteopontin in Wound Healing and Tissue Remodeling After Injury

Journal of Burn Care & Research ◽

10.1097/bcr.0b013e318240541e ◽

2012 ◽

Vol 33 (3) ◽

pp. 311-318 ◽

Cited By ~ 76

Author(s):

Cynthia E. Weber ◽

Neill Y. Li ◽

Philip Y. Wai ◽

Paul C. Kuo

Keyword(s):

Wound Healing ◽

Epithelial Mesenchymal Transition ◽

Tissue Remodeling ◽

Mesenchymal Transition

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Rosehip Oil Promotes Excisional Wound Healing by Accelerating the Phenotypic Transition of Macrophages

Planta Medica ◽

10.1055/a-0725-8456 ◽

2018 ◽

Vol 85 (07) ◽

pp. 563-569 ◽

Cited By ~ 1

Author(s):

Zhiyong Lei ◽

Zhijian Cao ◽

Zaiwang Yang ◽

Mingzhang Ao ◽

Wenwen Jin ◽

...

Keyword(s):

Wound Healing ◽

Epithelial Mesenchymal Transition ◽

New Drugs ◽

Mesenchymal Transition ◽

Excisional Wound ◽

Macrophage Phenotypes ◽

Immunohistological Staining ◽

Underlying Mechanisms ◽

Global Threat ◽

Phenotypic Transition

AbstractPoor wound healing is a major and global threat to public health. Efforts have been made to better understand the underlying mechanisms and develop effective remedies, though the advancements that have been made are still limited. As there are no effective and generally applicable therapies available for skin injuries and fibrosis, it is urgent to develop new drugs and therapies that facilitate wound healing and effectively improve scars. In this study, GC-MS analysis was performed to identify the chemical composition of rosehip oil. The excisional wound healing model and the carrageenan-induced paw edema method were respectively applied to evaluate the wound healing activity and anti-inflammatory activity of rosehip oil. Hematoxylin and eosin staining was used to assess the pathological changes of sections, and Sirius-red staining was performed to analyze the ratio of collagen I/III in wound tissues. Immunohistological staining for CD68, CCR7 (CD197), CD163, TGF-β1, and α-SMA was applied to determine the macrophage phenotypes transition (M1-to-M2) and demonstrate the scar-improving efficacy of rosehip oil on wound healing. Results showed that rosehip oil significantly promoted wound healing and effectively improved scars. This efficacy might be exerted by accelerating the macrophage phenotypes transition and inhibiting the process of epithelial-mesenchymal transition.

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Neuropilin 1 modulates TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer

10.21203/rs.2.10348/v1 ◽

2019 ◽

Author(s):

Zongli Ding ◽

Wenwen Du ◽

Zhe Lei ◽

Yang Zhang ◽

Jianjie Zhu ◽

...

Keyword(s):

Lung Cancer ◽

Wound Healing ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Migration And Invasion ◽

Wound Healing Assay ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Tgf Β1

Abstract Background: TGF-β1 signaling is a potent inducer of epithelial-mesenchymal transition (EMT) in various cancers. Our previous study has indicated that NRP1 was significantly up-regulated and acted as a vital promoter in the metastasis of non-small cell lung cancer (NSCLC). However, the function of NRP1 in regulation of TGF-β1-induced EMT and NSCLC cell migration and invasion remained unclear. Methods: The differential expression level of NRP1 was determined by RT-PCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine cell ability of migration. Lentivirus-mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF-β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanism. Results: Increased expression of NRP1 was found in metastatic NSCLC tissues and can promote NSCLC metastasis in vivo. Transwell assays, wound healing assay and western blot analysis showed that knockdown of NRP1 significantly inhibited TGF-β1-mediated EMT and migratory and invasive capabilities of A549 and H226 cells. Furthermore, overexpression of NRP1 could weak the decreased migratory and invasive capabilities with SIS3 treatment. Co-IP data showed that NRP1 can interact with TGFβRⅡ to induce EMT. Conclusion: This is the first time to report that NRP1 can modulate TGF-β1-induced EMT and cell migration and invasion in NSCLC.

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