Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness

Nakagawa, S; Pawelek, Pamela; Grinnell, Frederick

doi:10.1016/0014-4827(89)90260-7

Cited by 199 publications

(93 citation statements)

References 29 publications

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“…This observation is interesting because collagen or the composition of the extracellular matrix has been shown to regulate cell proliferation, migration, differentiation, and survival (Pickering, 2001). Collagen also acts as a repository for growth factors, changing their bioavailability and function (Nakagawa, Pawelek, & Grinnell, 1989). However, their excessive synthesis is pathological and negative for the regenerative process (Al‐Qattan, Abd‐Al Wahed, Hawary, Alhumidi, & Shier, 2014).…”

Section: Discussionmentioning

confidence: 99%

Limb regeneration in a direct‐developing terrestrial salamander, Bolitoglossa ramosi (Caudata: Plethodontidae)

et al. 2017

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Appendage regeneration is one of the most compelling phenomena in regenerative biology and is extensively studied in axolotls and newts. However, the regenerative capacity in other families of salamanders remains poorly described. Here we characterize the limb regeneration process in Bolitoglossa ramosi, a direct‐developing terrestrial salamander of the plethodontid family. We (1) describe the major morphological features at different stages of limb regeneration, (2) show that appendage regeneration in a terrestrial salamander varies from other amphibians and (3) show that limb regeneration in this species is considerably slower than in axolotls and newts (95 days post‐amputation for complete regeneration) despite having a significantly smaller genome size than axolotls or newts.

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Section: Discussionmentioning

confidence: 99%

Limb regeneration in a direct‐developing terrestrial salamander, Bolitoglossa ramosi (Caudata: Plethodontidae)

et al. 2017

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“…Previous studies have demonstrated that optimal fibroblast function (including growth and collagen production) depend on maintenance of the elongated cell shape. [43][44][45] Thus, it may be that loss of cell shape in the presence of degraded collagen directly underlies reduced growth and collagen production on the partially degraded collagen gels. Based on the in vivo ultrastructural findings presented here, we suggest that loss of cell shape could underlie reduced collagen synthesis in severely photodamaged skin.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Varani

Spearman

Perone

et al. 2001

The American Journal of Pathology

290

208

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Type I and type III procollagen are reduced in photodamaged human skin. This reduction could result from increased degradation by metalloproteinases and/or from reduced procollagen synthesis. In the present study, we investigated type I procollagen production in photodamaged and sun-protected human skin. Skin samples from severely sun-damaged forearm skin and matched sun-protected hip skin from the same individuals were assessed for type I procollagen gene expression by in situ hybridization and for type I procollagen protein by immunostaining. Both mRNA and protein were reduced (ϳ65 and 57%, respectively) in photodamaged forearm skin compared to sun-protected hip skin. We next investigated whether reduced type I procollagen production was because of inherently reduced capacity of skin fibroblasts in severely photodamaged forearm skin to synthesize procollagen, or whether contextual influences within photodamaged skin act to down-regulate type I procollagen synthesis. For these studies, fibroblasts from photodamaged skin and matched sunprotected skin were established in culture. Equivalent numbers of fibroblasts were isolated from the two skin sites. Fibroblasts from the two sites had similar growth capacities and produced virtually identical amounts of type I procollagen protein. These findings indicate that the lack of type I procollagen synthesis in sun-damaged skin is not because of irreversible damage to fibroblast collagen-synthetic capacity. It follows, therefore, that factors within the severely photodamaged skin may act in some manner to inhibit procollagen production by cells that are inherently capable of doing so. Interactions between fibroblasts and the collagenous extracellular matrix regulate type I procollagen synthesis. In sun-protected skin, collagen fibrils exist as a highly organized matrix. Fibroblasts are found within the matrix, in close apposition with collagen fibers. In photodamaged skin, collagen fibrils are shortened, thinned, and disorganized. The level of partially degraded collagen is ϳ3.6-fold greater in photodamaged skin than in sun-protected skin, and some fibroblasts are surrounded by debris. To model this situation, skin fibroblasts were cultured in vitro on intact collagen or on collagen that had been partially degraded by exposure to collagenolytic enzymes. Collagen that had been partially degraded by exposure to collagenolytic enzymes from either bacteria or human skin underwent contraction in the presence of dermal fibroblasts, whereas intact collagen did not. Fibroblasts cultured on collagen that had been exposed to either source of collagenolytic enzyme demonstrated reduced proliferative capacity (22 and 17% reduction on collagen degraded by bacterial collagenase or human skin collagenase, respectively) and synthesized less type I procollagen (36 and 88% reduction, respectively, on a per cell basis). Taken together, these findings indicate that 1) fibroblasts from photoaged and sun-protected skin are similar in their capacities for growth and type I procollagen productio...

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“…Subsequently, cells show marked changes in growth factor receptor function and biosynthetic activity (e.g., decreased synthesis of collagen) and become quiescent (39,45,46…”

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confidence: 99%

“…Subsequently, cells show marked changes in growth factor receptor function and biosynthetic activity (e.g., decreased synthesis of collagen) and become quiescent (39,45,46). During the initial moments of contraction, cells transiently open passages ϳ3 nm in diameter in their plasma membranes, resulting in a burst of Ca 2ϩ uptake from the medium (38).…”

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confidence: 99%

Increased c-fos mRNA Expression By Human Fibroblasts Contracting Stressed Collagen Matrices

Rosenfeldt

Lee

Grinnell

1998

Molecular and Cellular Biology

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We studied early changes in gene expression during fibroblast contraction of stressed collagen matrices. The level of c-fos mRNA increased dramatically and peaked 50 to 60 min after matrix contraction was initiated. This response did not require serum and could not be accounted for simply by disruption of the actin cytoskeleton. Increased c-fos mRNA levels required Ca 2؉ influx but not the cyclic AMP or extracellular signal-regulated kinase (ERK 1/2) signaling pathways, both of which are activated when fibroblasts contract stressed collagen matrices. The levels of two other immediate-early genes, fosb and c-jun, also increased transiently after fibroblast contraction, whereas the levels of fra-1, fra-2, c-myc, and the transcription factor NF-B remained the same, indicating that fibroblast contraction caused changes in a selective group of genes. The increase in c-fos mRNA during contraction of stressed collagen matrices may reflect a unique role for c-fos in mechanoregulated events at the end of wound repair.Mechanical force influences cell function in animal and plant tissues (6,11,30,67). For instance, increased mechanical load, such as fluid flow over endothelial cells or tension applied to muscle cells, has been shown to result in cell proliferation or hypertrophy (15, 64). During wound repair, mechanical force within the wound tissue pulls the wound edges closer together, which in pathological cases results in scarring and loss of function (29, 52). Wound contraction is believed to be mediated by fibroblasts as they go through a cycle of migration, proliferation, contraction, and regression (13,40).Fibroblasts cultured in collagen matrices have been used as an in vitro model for wound contraction (3,20). In this model, cells reorganize the extracellular matrix through migratory and contractile activities (3, 25), resulting in formation of a dense, tissue-like structure. The fibroblast phenotype that develops during collagen matrix reorganization differs dramatically depending upon whether collagen matrices are floating in medium or attached to a rigid support. After reorganization of attached matrices, the cells resemble proliferating fibroblasts of wound tissue under mechanical stress and are characterized by polarized morphology, prominent stress fibers, and fibronexus junctions (23,37,45,62). Cells in attached collagen matrices exert force on the matrix similar to that observed in contracting skin wounds (12, 34). After reorganization of floating matrices, on the other hand, cells resemble nondividing fibroblasts of resting dermis or scar tissue in a state of mechanical equilibrium and are characterized by isometric (stellate) cell morphology and cytoskeletal meshwork (3, 4).We have combined the attached and floating models to study the regulatory events associated with the transition of fibroblasts from mechanically stressed to mechanically equilibrated conditions (stress-relaxation) such as occurs by the end of wound repair. Initially, fibroblasts are cultured in attached collagen matrices until mechan...

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Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness

Cited by 199 publications

References 29 publications

Limb regeneration in a direct‐developing terrestrial salamander, Bolitoglossa ramosi (Caudata: Plethodontidae)

Limb regeneration in a direct‐developing terrestrial salamander, Bolitoglossa ramosi (Caudata: Plethodontidae)

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Increased c-fos mRNA Expression By Human Fibroblasts Contracting Stressed Collagen Matrices

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