Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform

Zhang, Tianzi; Day, John H.; Su, Xiaojing; Guadarrama, Arturo G.; Sandbo, Nathan; Esnault, Stéphane; Denlinger, Loren C.; Berthier, Jean; Theberge, Ashleigh B.

doi:10.3389/fbioe.2019.00196

Cited by 34 publications

(22 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We therefore wondered whether dysadherin serves as a regulator of mechanical force. The collagen gel contraction assay 37 , 38 has served as a classic tool in the field of mechanobiology to study cell-induced contraction of the ECM, which plays an important role in tumor progression and aggression 39 . We analyzed the extent of gel contraction upon dysadherin OE and KO using this assay.…”

Section: Resultsmentioning

confidence: 99%

Dysadherin awakens mechanical forces and promotes colorectal cancer progression

Park¹,

Lee²,

Choi³

et al. 2022

Theranostics

View full text Add to dashboard Cite

Rationale : Dysadherin is a tumor-associated, membrane-embedded antigen found in multiple types of cancer cells, and associated with malignant behavior of cancer cells; however, the fundamental molecular mechanism by which dysadherin drives aggressive phenotypes of cancer is not yet fully determined. Methods : To get a mechanistic insight, we explored the physiological relevance of dysadherin on intestinal tumorigenesis using dysadherin knockout mice and investigated its impact on clinicopathological features in patients with advanced colorectal cancer (CRC). Next, to discover the downstream signaling pathways of dysadherin, we applied bioinformatic analysis using gene expression data of CRC patient tumors and dysadherin knockout cancer cells. Additionally, comprehensive proteomic and molecular analyses were performed to identify dysadherin-interacting proteins and their functions. Results : Dysadherin deficiency suppressed intestinal tumorigenesis in both genetic and chemical mouse models. Moreover, increased dysadherin expression in cancer cells accounted for shorter survival in CRC patients. Comprehensive bioinformatics analyses suggested that the effect of dysadherin deletion is linked to a reduction in the extracellular matrix receptor signaling pathway. Mechanistically, the extracellular domain of dysadherin bound fibronectin and enhanced cancer cell adhesion to fibronectin, facilitating the activation of integrin-mediated mechanotransduction and leading to yes-associated protein 1 activation. Dysadherin-fibronectin interaction promoted cancer cell growth, survival, migration, and invasion, effects collectively mediated the protumor activity of dysadherin. Conclusion : Our results highlight a novel function of dysadherin as a driver of mechanotransduction that stimulates CRC progression, providing a potential therapy strategy for CRC.

show abstract

Section: Resultsmentioning

confidence: 99%

Dysadherin awakens mechanical forces and promotes colorectal cancer progression

Park¹,

Lee²,

Choi³

et al. 2022

Theranostics

View full text Add to dashboard Cite

show abstract

“…Either way, these experiments demonstrate versatility of this model. While cells, 56 , 57 including IVD cells, 38 , 39 have been previously cultured in collagen in various forms, our model explains a relatively easy and versatile matrix that can be used for not only mechanical testing but also the interplay between inflammation and mechanics for AF cells, which then provides insight into the functional impact of structural changes. Another hypothesis could be that adding LPS to cells+collagen constructs has caused an increase in matrix metalloproteinases (MMPs) secretion which in turn has affected matrix molecules.…”

Section: Discussionmentioning

confidence: 99%

An in vitro 3D annulus fibrosus cell culture model with type I collagen: An examination of cell–matrix interactions

2022

View full text Add to dashboard Cite

Background: Disorders of the intervertebral disc (IVD) are widely known to result in low back pain; one of the most common debilitating conditions worldwide. As a multifaceted condition, both inflammatory environment and mechanical factors can play a crucial role in IVD damage, and in particular, in the annulus fibrosus (AF), the highly collagenous outer ring of the IVD. As a result, a better understanding of how cells from the IVD, and specifically the AF, interact and respond to their environment is imperative. Goal:The goal of this study is to use collagen type I as an in vitro three-dimensional extracellular matrix for AF cells of IVD and briefly examine both the cellular and mechanical effect of exposure to an inflammatory stimulant.Methods: We utilized type I collagen as a 3D in vitro model material for culturing AF cells of Sprague Dawley rat tail IVDs.Results: We showed that the cultured cells are viable and metabolically active; these cells also induced a distinct and significant contraction on their collagen matrix. Furthermore, to demonstrate potential versatility of our model our model and its versatility, we used lipopolysaccharide (LPS), as a known inflammatory stimulant in IVDs, to manipulate the cells and their interaction. LPS treatment resulted in detectable changes to the contraction cells induced on the collagen matrix and affected the mechanical properties of these constructs.

show abstract

“…The critical point in the pathogenesis of PVR is the contraction of cell membranes, which promotes retinal detachment and, in turn, leads to vision loss [ 44 ]. Collagen gel contraction is the classic model for studying wound healing [ 45 ], a process in which the main cell types are fibroblasts and transdifferentiated RPE cells [ 46 – 48 ]. In the present study, possibly because of reduced α-SMA and vimentin expression and increased ZO-1 expression, miR-1285 reduced collagen gel contraction in ARPE-19 cells treated with TGF-β2.…”

Section: Discussionmentioning

confidence: 99%

Repression of Smad4 by MicroRNA-1285 moderates TGF-β-induced epithelial–mesenchymal transition in proliferative vitreoretinopathy

et al. 2021

View full text Add to dashboard Cite

The purpose of this study was to assess whether microRNA (miR)-1285 can suppress the epithelial–mesenchymal transition (EMT) in retinal pigment epithelial cells. Expression of miR-1285 was evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). The features of EMT were assessed using Western blotting, immunocytochemical staining, scratch wound healing tests, modified Boyden chamber assay, and collagen gel contraction assay. A rabbit model of proliferative vitreoretinopathy (PVR) was used for in vivo testing, which involved the induction of PVR by injection of transfected ARPE cells into the vitreous chamber. Luciferase reporter assay was performed to identify the putative target of miR-1285. The expression of miR-1285 was downregulated in ARPE-19 cells treated with transforming growth factor (TGF)-β. Overexpression of miR-1285 led to upregulation of zonula occludens-1, downregulation of α-smooth muscle actin and vimentin, cell migration and cell contractility—all EMT features—in the TGF-β2-treated ARPE-19 cells. The reporter assay indicated that the 3′ untranslated region of Smad4 was the direct target of miR1285. PVR progression was alleviated in the miR-1285 transfected rabbits. In conclusion, overexpression of miR-1285 attenuates TGF-β2-induced EMT in a rabbit model of PVR, and the effect of miR-1285 in PVR is dependent on Smad4. Further research is warranted to develop a feasible therapeutic approach for the prevention and treatment of PVR.

show abstract

Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform

Cited by 34 publications

References 45 publications

Dysadherin awakens mechanical forces and promotes colorectal cancer progression

Dysadherin awakens mechanical forces and promotes colorectal cancer progression

An in vitro 3D annulus fibrosus cell culture model with type I collagen: An examination of cell–matrix interactions

Repression of Smad4 by MicroRNA-1285 moderates TGF-β-induced epithelial–mesenchymal transition in proliferative vitreoretinopathy

Contact Info

Product

Resources

About