ABSTRACT Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid cyclooxygenases (COX) synthases (PGES), acts as both an mediator modulator. Although PGE2 known antifibrotic effects in the lower airway, its role dermal fibrosis general, keloid particular, remains unclear. This study focused on: (1) of on migration, contraction, collagen synthesis (2) endogenous...

Long-term clinical outcomes are dependent on whether carcinoma cells leave the primary tumor site and invade through adjacent tissue. Recent evidence links tissue rigidity to alterations in cancer cell phenotype progression. We found that rigid extracellular matrix (ECM) substrates promote invasiveness of via increased activity invadopodia, subcellular protrusions with associated ECM-degrading proteinases. Although mechanism by which substrate promotes invadopodia function remains be...

To test urinary bladder matrix (UBM) as a potential treatment for tympanic membrane (TM) healing and regeneration.This prospective pilot study was designed to provide both qualitative semiquantitative assessment of temporal spatial events in the chinchilla model chronic TM perforations with without UBM patching.Bilateral myringotomies were performed repeated necessary create subtotal over an 8-week period. Myringoplasty then performed, left TMs serving controls right receiving patches....

Heart valve interstitial cells (VICs) appear to have a dynamic and reversible phenotype, an attribute speculated be necessary for tissue remodeling during times of development repair. Therefore, we hypothesized that the cytoskeletal (CSK) capability aortic pulmonary VICs (AVICs PVICs, respectively), which are dominated by smooth muscle α-actin, would exhibit unique contractile behaviors when seeded on collagen gels. Using porcine cell source, observed VIC populations did not contract gels at...

Cadherin-11 (CDH11) is upregulated in a variety of fibrotic diseases, including arthritis and calcific aortic valve disease. Our recent work has identified CDH11 as potential therapeutic target shown that treatment with functional blocking antibody can prevent hallmarks disease mice. The present study investigated the role regulating mechanobiological behavior valvular interstitial cells believed to cause calcification. Aortic were harvested from Cdh11+/+, Cdh11+/-, Cdh11-/- immortomice....

ABSTRACT Cyclooxygenase‐2 is up‐regulated shortly after dermal injury and it has been shown to have important activity during the repair process. Its main product in skin, prostaglandin E2 (PGE2), modulates both inflammatory fibrotic processes wound healing partially dictates overall outcome of healing. PGE2 signaling be altered fetal This study was designed examine mechanism(s) by which regulates fibroblast migration contraction determine whether these mechanisms are conserved fetal‐derived...

ABSTRACT Contraction and remodeling of granulation tissue by fibroblasts is a crucial component dermal wound healing. Postnatal wounds heal with imperfect repair scar formation, whereas in fetal regenerative. Prostaglandin E2 (PGE2) modulates the behavior bed. This study was designed to investigate mechanism which PGE2 regulates an vitro model tissue, anchored collagen gels, human adult fibroblasts. We hypothesized that differentially contraction gels these fibroblast phenotypes. These...

Successful approaches to tissue engineering smooth muscle tissues utilize biodegradable scaffolds seeded with autologous cells. One common problem in using biological specifically is the difficulty of inducing cellular penetration and controlling de novo extracellular matrix deposition/remodeling vitro. Our hypothesis was that small intestinal submucosa (SIS) exposed specific mechanical stimulation regimes would modulate synthesis collagen elastin by bladder cells (BSMC) within SIS matrix....

Fetal dermal fibroblasts participate in a dramatically different wound healing process compared to their adult counterparts, and it is thought that intrinsic phenotype contributes the unique properties of fetal repair. In particular, fibroblast migratory contractile have been shown be important development or lack fibrosis/scarring. Despite extensive study date, multiple experimental techniques utilized by various laboratories, precise differences between remain unclear. We characterized...

In contrast to fetal wound healing, dermal adult healing results in imperfect repair and scar formation. Fibroblasts are responsible for the contraction remodeling of matrix, which is influenced by inflammatory mediators including prostaglandin E2 (PGE2). This study addresses mechanism PGE2 regulates collagen gels human fibroblasts. We hypothesized that intrinsic phenotypic properties two types fibroblasts their responses alter contribute different outcomes. Contraction was evaluated using...

Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK cause a switch these phenotypes which are defined by distinct morphologies. However, recent studies have shown that the isoforms not functionally redundant as previously thought. Therefore, it is unclear whether play different roles regulating phenotypes. Here, we found ROCK1...

Abstract During the dermal wound healing process, mechanical rigidity of newly deposited extracellular matrix and transforming growth factor‐β1 promote transition fibroblasts into myofibroblasts. Myofibroblasts generate large cellular forces that contract remodel leading to scar formation. In contrast, myofibroblasts are not detected in fetal wounds which more compliant contain less than adult wounds. Instead, orchestrate scarless resulting healed tissues resemble uninjured dermis. While...

Modulation of the bladder smooth muscle cell phenotype contributes to resulting dysfunction in many pathological conditions. Transforming growth factor-beta1 is an important regulator cellular fibrotic diseases that has specific effects on cells associated with phenotypic changes. We verified transforming expression neurogenic tissue and investigated its collagen gel contraction.Transforming immunostaining was performed sections from spinalized rats quantified based ratio fluorescence total...

Pathological alterations in the relationship between cells and extracellular matrix have a profound effect on tissue morphology function. Transforming growth factor-beta1 is thought to role bladder pathology by modulating smooth muscle cell phenotype and, thus, interactions with matrix. We investigated effects of transforming organization an vitro cells.Rat were seeded at different densities (5 x 10(4), 1 10(5) 2.5 cells) anchored collagen gels allowed contract for 18 or 24 hours. assessed...

Rigid tumor tissues have been strongly implicated in regulating cancer cell migration and invasion. Invasive through cross-linked is facilitated by actin-rich protrusions called invadopodia that proteolytically degrade the extracellular matrix (ECM). Invadopodia activity has shown to be dependent on ECM rigidity contractile forces suggesting signals can regulate these subcellular structures actomyosin contractility. properties of cells correlated vitro using traction force assays based...