PERSISTENCE OF TGF-β1 INDUCTION OF INCREASED FIBROBLAST CONTRACTILITY

Liu, X. D.; Umino, Takeshi; Ertl, Ronald F.; Veys, Tom; Sköld, C. Magnus; Takigawa, Keiichi; Romberger, Debra J.; Spurzem, John R.; Zhu, Yun; Kohyama, Tadashi; Wang, H.; Rennard, Stephen I.

doi:10.1290/1071-2690(2001)037<0193:potioi>2.0.co;2

Cited by 28 publications

(30 citation statements)

References 35 publications

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“…Moreover, in vitro exposure to exogenous TGF-b1 stimulated all of the bioassays assessed in the current study. The in vitro effects of TGF-b, however, have been reported to be transient in contrast to the persistent phenotypic alterations observed in cells obtained from patients with asthma and from animals (22), suggesting that the differences between OVA-challenged and control mouse cells are not the result of TGF-b production by the OVA-challenged mouse cells. In addition, in the current study, both control and OVA-challenged mouse cells demonstrated the ability to respond to exogenous TGF-b (100 pM).…”

Section: Discussionmentioning

confidence: 95%

“…In this context, airway parenchymal cells can respond to mediators present in the inflammatory milieu of the asthmatic airway. Both Th2 cytokines and TGF-b, for example, can have ''profibrotic'' effects on target mesenchymal cells, including the induction of a-SMA and other myofibroblast-like features in fibroblasts (21,22). Thus, inflammatory mediators may contribute to the structural changes present in the airway.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-b has been associated with expression of myofibroblastlike features in fibroblasts (22). Other conditions of culture, such as serum (36) or culture on a solid substrate (37) also induce a-SMA expression.…”

Section: Discussionmentioning

confidence: 99%

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Cultured Lung Fibroblasts from Ovalbumin-Challenged “Asthmatic” Mice Differ Functionally from Normal

Sugiura

Liu

Duan

et al. 2007

Am J Respir Cell Mol Biol

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Asthmatic airway remodeling is characterized by goblet cell hyperplasia, angiogenesis, smooth muscle hypertrophy, and subepithelial fibrosis. This study evaluated whether acquired changes in fibroblast phenotype could contribute to this remodeling. Airway and parenchymal fibroblasts from control or chronically ovalbumin (OVA)-sensitized and challenged ''asthmatic'' mice were assessed for several functions related to repair and remodeling 6 exogenous transforming growth factor (TGF)-b. All OVA-challenged mouse fibroblasts demonstrated augmented gel contraction (P , 0.05) and chemotaxis (P , 0.05); increased TGF-b 1 (P , 0.05), fibronectin (P , 0.05), and vascular endothelial growth factor (P , 0.05) release; and expressed more a-smooth muscle actin (P , 0.05). TGF-b 1 stimulated both control and asthmatic fibroblasts, which retained all differences from control fibroblasts for all features(P , 0.05, all comparisons). Parenchymal fibroblasts proliferated more rapidly (P , 0.05), while airway fibroblasts proliferated similarly compared with control fibroblasts (P 5 0.25). Thus, in this animal model, OVAchallenged mouse fibroblasts acquire a distinct phenotype that differs from control fibroblasts. The augmented profibrotic activity and mediator release of asthmatic fibroblasts could contribute to airway remodeling in asthma.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cultured Lung Fibroblasts from Ovalbumin-Challenged “Asthmatic” Mice Differ Functionally from Normal

Sugiura

Liu

Duan

et al. 2007

Am J Respir Cell Mol Biol

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“…Expression of TGF-␤1 is associated with Journal of Cell Science 119 (24) many key events in the wound healing process: it is a potent immunosuppressive (Wahl, 1992); it can promote fibroblast migration and proliferation (Postlethwaite et al, 1987); enhance wound contraction (Beck et al, 1991;Liu et al, 2001); enhance granulation tissue formation through ␣-SMA in myofibroblasts (Desmouliere et al, 1993), enhance collagen synthesis and deposition (Shah et al, 1994), stimulate angiogenesis (Roberts et al, 1986) and promote reepithelialization (Chesnoy et al, 2003). There remains a good deal of confusion associated with the effect TGF-␤1 has when applied directly to the wound, different results being obtained depending on dosage and wounding model (Hebda et al, 1988;Mustoe et al, 1991;Garlick and Taichman, 1994).…”

Section: Tgf-␤1mentioning

confidence: 99%

Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration

Mori

Power

Wang

et al. 2006

Journal of Cell Science

224

245

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myofibroblast differentiation and wound contraction appeared to be advanced by 2-3 days. Recruitment of both neutrophils and macrophages was markedly reduced within treated wounds, concomitant with reduced leukocyte infiltration. In turn, mRNA levels of CC chemokine ligand 2 and TNF-␣ were reduced in the treated wound. These data suggest that, by reducing Cx43 protein with Cx43-specific antisense oligodeoxynucleotides at wound sites early in the skin healing process repair is enhanced, at least in part, by accelerating cell migration and proliferation, and by attenuating inflammation and the additional damage it can cause. Journal of Cell Science 5194 the wound and lay down collagen matrix. We observed a decrease in neutrophil infiltration and a concomitant reduction in CC chemokine ligand 2 (Ccl2) and cytokine tumor necrosis factor ␣ (TNF-␣) mRNA. Subsequently, we saw a reduced recruitment of macrophages perhaps as a consequence of damping down of the initial inflammatory response, which is known to have downstream effects on the ensuing healing process. Together these modified responses resulted in significantly improved wound healing. ResultsDownregulation of Cx43 at wound sites with Cx43-asODN As previously reported, Cx43 was found to be predominantly expressed in the lower and middle spinous cell layers of the epidermis and in fibroblasts, blood vessels and dermal appendages of intact skin. Six hours after the injury Cx43 was expressed in hyperproliferative epidermis but began to be downregulated in the leading edge keratinocytes (Goliger and Paul, 1995;Coutinho et al., 2003). Delivery of Cx43-asODN from the time of injury markedly reduced protein levels of Cx43 in the epidermis and dermis within 2 hours of treatment (as revealed by immunohistochemistry) (Qiu et al., 2003). Such a rapid knockdown is possible because Cx43 protein is turned over rapidly, sometimes within 1.5-2 hours (Laird et al., 1991; Gaitta et al., 2002). To quantify the extent of Cx43 protein and mRNA knockdown and recovery after asODN treatment more precisely, we compared expression levels of Cx43 mRNA at treated and untreated wound sites by real-time PCR (RT-PCR; Fig. 1). One day after injury, expression of Cx43 mRNA at Cx43-asODN-treated wounds was significantly reduced by comparison with control sODN-treated wounds (2.95 versus 4.7 units, respectively, a 37% reduction; P<0.05). By 7 days after the injury, however, expression levels were similar in the two wound regimes (4.6 versus 5.2 units for asODN-and control sODN-treated, respectively). Immunostaining of wounds for Cx43 at 1 day, 2 days and 7 days after wounding revealed very low levels of Cx43 protein in the epidermis and dermis of the Cx43-asODN-treated wound edge at day 1 compared with controls ( Fig. 1). By day 2, some Cx43 staining had returned to the dermis of the Cx43-asODN-treated wound but the level was still very low in the epidermis. By day 7, in agreement with the RT-PCR findings, there was no obvious difference in Cx43 staining between treated and untreated wounds. T...

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“…To study how growth factors might affect stability, we examined the effects of TGF-b1, a known enhancer of fibroblast contractility 20 ( Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

Micro-Mold Design Controls the 3D Morphological Evolution of Self-Assembling Multicellular Microtissues

Svoronos

Tejavibulya

Schell

et al. 2014

Tissue Engineering Part A

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When seeded into nonadhesive micro-molds, cells self-assemble three-dimensional (3D) multicellular microtissues via the action of cytoskeletal-mediated contraction and cell-cell adhesion. The size and shape of the tissue is a function of the cell type and the size, shape, and obstacles of the micro-mold. In this article, we used human fibroblasts to investigate some of the elements of mold design and how they can be used to guide the morphological changes that occur as a 3D tissue self-organizes. In a loop-ended dogbone mold with two nonadhesive posts, fibroblasts formed a self-constrained tissue whose tension induced morphological changes that ultimately caused the tissue to thin and rupture. Increasing the width of the dogbone's connecting rod increased the stability, whereas increasing its length decreased the stability. Mapping the rupture points showed that the balance of cell volume between the toroid and connecting rod regions of the dogbone tissue controlled the point of rupture. When cells were treated with transforming growth factor-b1, dogbones ruptured sooner due to increased cell contraction. In mold designs to form tissues with more complex shapes such as three interconnected toroids or a honeycomb, obstacle design controlled tension and tissue morphology. When the vertical posts were changed to cones, they became tension modulators that dictated when and where tension was released in a large self-organizing tissue. By understanding how elements of mold design control morphology, we can produce better models to study organogenesis, examine 3D cell mechanics, and fabricate building parts for tissue engineering.

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PERSISTENCE OF TGF-β1 INDUCTION OF INCREASED FIBROBLAST CONTRACTILITY

Cited by 28 publications

References 35 publications

Cultured Lung Fibroblasts from Ovalbumin-Challenged “Asthmatic” Mice Differ Functionally from Normal

Cultured Lung Fibroblasts from Ovalbumin-Challenged “Asthmatic” Mice Differ Functionally from Normal

Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration

Micro-Mold Design Controls the 3D Morphological Evolution of Self-Assembling Multicellular Microtissues

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