Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40)

Basu, Amitabha; Kligman, Lorraine H.; Samulewicz, Stefan; Howe, Chin C.

doi:10.1186/1471-2121-2-15

Cited by 87 publications

(34 citation statements)

References 32 publications

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“…Extracellular constituents such as fibronectin (16) and laminin (17) have been shown to stimulate re-epithelisation in the wound environment. In our model, expression of both fibronectin and laminin was similar in all three dermal populations; however, the secreted protein SPARC that is linked to tissue repair and remodelling (18)(19)(20) was expressed more highly by follicle dermal cells. This suggested that SPARC may play a key role in keratinocyte support.…”

Section: Discussionmentioning

confidence: 89%

Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer coculture

Hill

Gardner

Crawford

et al. 2013

Experimental Dermatology

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Additional Supporting Information may be found in the online version of this article: Figure S1. Sequence comparison between Foxq1+/+ (top) and Foxq1 (bottom) genes. Note the C to T transition at nucleotide 490 between the control (top) and mutant (bottom) alleles. Abstract: Traditional skin grafting techniques are effective but limited methods of skin replacement. Autologous transplantation of rapidly cultured keratinocytes is successful for epidermal regeneration, but the current gold-standard technique requires mouse fibroblast feeders and serum-rich media, with serum-free systems and dermal fibroblast (DF) feeders performing relatively poorly. Here, we investigated the capacity of human hair follicle dermal cells to act as alternative supports for keratinocyte growth. Dermal papilla (DP) dermal sheath (DS), DF and 3T3 cells were used as inactivated feeder cells for human keratinocyte coculture. Under conditions favouring dermal cells, proliferation of keratinocytes in the presence of either DS or DP cells was significantly enhanced compared with DF cells, at levels comparable to keratinocytes cultured under gold-standard conditions. Secreted protein acidic and rich in cysteine (SPARC) expression increased DS and DP cells relative to DFs; however, further experiments did not demonstrate a role in keratinocyte support.

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Section: Discussionmentioning

confidence: 89%

Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer coculture

Hill

Gardner

Crawford

et al. 2013

Experimental Dermatology

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“…Although SPARC expression is markedly and consistently upregulated in healing tissues (360), (359), loss-of-function studies have provided conflicting results on its role. In large excisional cutaneous wounds, Basu and co-workers demonstrated that SPARC absence is associated with impaired and delayed healing; the defect was restored by administration of purified SPARC (31). In contrast, Bradshaw and colleagues demonstrated accelerated skin wound closure in SPARC null animals resulting from enhanced contractibility of the collagen-poor scar (55).…”

Section: The Matricellular Proteins Key Modulators Of Cell:cellmentioning

confidence: 99%

Matricellular Proteins in Cardiac Adaptation and Disease

Frangogiannis

2012

Physiological Reviews

378

375

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The term matricellular proteins describes a family of structurally unrelated extracellular macromolecules that, unlike structural matrix proteins, do not play a primary role in tissue architecture, but are induced following injury and modulate cell-cell and cell-matrix interactions. When released to the matrix, matricellular proteins associate with growth factors, cytokines, and other bioactive effectors and bind to cell surface receptors transducing signaling cascades. Matricellular proteins are upregulated in the injured and remodeling heart and play an important role in regulation of inflammatory, reparative, fibrotic and angiogenic pathways. Thrombospondin (TSP)-1, -2, and -4 as well as tenascin-C and -X secreted protein acidic and rich in cysteine (SPARC), osteopontin, periostin, and members of the CCN family (including CCN1 and CCN2/connective tissue growth factor) are involved in a variety of cardiac pathophysiological conditions, including myocardial infarction, cardiac hypertrophy and fibrosis, aging-associated myocardial remodeling, myocarditis, diabetic cardiomyopathy, and valvular disease. This review discusses the properties and characteristics of the matricellular proteins and presents our current knowledge on their role in cardiac adaptation and disease. Understanding the role of matricellular proteins in myocardial pathophysiology and identification of the functional domains responsible for their actions may lead to design of peptides with therapeutic potential for patients with heart disease.

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“…In adult tissues, expression of SPARC is highest in tissues undergoing active matrix remodeling, where it is hypothesized to function as a negative regulator of growth factor activity and has been shown to possess antiadhesive and antiproliferative properties (Lane and Sage 1994;Brown et al 2006;Martinek et al 2007). SPARC-null mice exhibit several features characteristic of premature senescence: early onset cataractogenesis (Gilmour et al 1998), impaired wound healing (Basu et al 2001), accelerated osteoporosis, and spinal discs degeneration (Delany et al 2003;Gruber et al 2005), indicating a general role for the protein in both the maintenance and remodeling of ECM.…”

Section: Introductionmentioning

confidence: 99%

Recombinant mouse SPARC promotes parietal endoderm differentiation and cardiomyogenesis in embryoid bodies

Hrabchak

Ringuette

Woodhouse

2008

Biochem. Cell Biol.

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In the absence of leukemia inhibitory factor, murine embryonic stem cells cultured in vitro spontaneously aggregate to from three-dimensional embryoid bodies that differentiate to produce hematopoietic, endothelial, muscle, and neuronal cell lineages in a manner recapitulating the events of early embryogenesis. Cardiomyogenesis in embryoid bodies was recently demonstrated to be promoted by PYS-2-derived native SPARC (secreted protein, acidic and rich in cysteine), whose expression is upregulated in parietal endoderm at the onset of the epithelial to mesenchymal transition. Here, we confirm the stimulatory effects of mouse SPARC on cardiomyogenesis using a recombinant baculovirus-produced protein (rmSPARC). Embryoid bodies cultured in the presence of glycosylated rmSPARC, or an unglycosylated peptide spanning the C-terminal EF-hand domain, developed greater numbers of beating cardiomyocytes than did time-matched controls, with enhanced expression of cardiac marker genes including Nkx2.5, Troponin, BMP-2, and MHCalpha. Histochemical analysis revealed an expansion of the peripheral endoderm, with thicker layers of extracellular matrix (ECM) material observed atop underlying cells. Embryoid bodies treated with SPARC also displayed increased adherence to polystyrene culture dishes, with enhanced expression of ECM mRNAs including collagen IValpha3, collagen IValpha5, and laminin alpha1. These results indicate that, in addition to the promotion of cardiomyogenesis, SPARC may also help regulate the molecular composition and organization of ECM secreted by the mesenchymal parietal endoderm.

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Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40)

Cited by 87 publications

References 32 publications

Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer coculture

Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer coculture

Matricellular Proteins in Cardiac Adaptation and Disease

Recombinant mouse SPARC promotes parietal endoderm differentiation and cardiomyogenesis in embryoid bodies

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