Expression of the Matricellular Protein SPARC in Murine Lens: SPARC Is Necessary for the Structural Integrity of the Capsular Basement Membrane

Yan, Qi; Blake, David A.; Clark, John I.; Sage, E. Helene

doi:10.1177/002215540305100412

Cited by 37 publications

(31 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Disruption of this attachment causes defects in cortical lamination, such as in mice with genetic defects in integrins, ILK, FAK, and ECM components (Graus-Porta et al, 2001;Halfter et al, 2002;Beggs et al, 2003;Poschl et al, 2004;Niewmierzycka et al, 2005). SPARC could potentially act to anchor radial glial endfeet, either by modulating the stability of focal adhesions via integrin-mediated FAK and ILK signaling (Shi et al, 2007), or alternatively by the assembly and maintenance of ECM components in the basement membrane (Yan et al, 2003). SPARC, which remains enriched in endfeet, may continue to stabilize radial glial morphology in the adult, such as in the cerebellum and retina (Fig.…”

Section: Discussionmentioning

confidence: 99%

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Vincent

Lau

Roskams

2008

Developmental Dynamics

View full text Add to dashboard Cite

SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that is highly expressed during development, tissue remodeling, and repair. SPARC produced by olfactory ensheathing cells (OECs) can promote axon sprouting in vitro and in vivo. Here, we show that in the developing nervous system of the mouse, SPARC is expressed by radial glia, blood vessels, and other pial-derived structures during embryogenesis and postnatal development. The rostral migratory stream contains SPARC that becomes progressively restricted to the SVZ in adulthood. In the adult CNS, SPARC is enriched in specialized radial glial derivatives (Mü ller and Bergmann glia), microglia, and brainstem astrocytes. The peripheral glia, Schwann cells, and OECs express SPARC throughout development and in maturity, although it appears to be down-regulated with maturation. These data suggest that SPARC may be expressed by glia in a spatiotemporal manner consistent with a role in cell migration, neurogenesis, synaptic plasticity, and angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Vincent

Lau

Roskams

2008

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…SPARC might function to reduce lens epithelial cell binding to collagen IV, another SPARC-binding collagen. Immunohistochemistry of lens basement membrane from SPARC-null mice demonstrated disorganized collagen IV associated with ␤ 1 integrin-positive cellular protrusions into the matrix (38). Failure of lens epithelial cells to release collagen IV from ␤ 1 integrin engagement might contribute to the disorganized basal lamina in SPARC-null lens.…”

Section: H (F and E)mentioning

confidence: 96%

SPARC Regulates Processing of Procollagen I and Collagen Fibrillogenesis in Dermal Fibroblasts

Rentz

Poobalarahi

Börnstein

et al. 2007

Journal of Biological Chemistry

Self Cite

147

134

View full text Add to dashboard Cite

A characterization of the factors that control collagen fibril formation is critical for an understanding of tissue organization and the mechanisms that lead to fibrosis. SPARC (secreted protein acidic and rich in cysteine) is a counter-adhesive protein that binds collagens. Herein we show that collagen fibrils in SPARC-null skin from mice 1 month of age were inefficient in fibril aggregation and accumulated in the diameter range of 60 -70 nm, a proposed intermediate in collagen fibril growth. In vitro, procollagen I produced by SPARC-null dermal fibroblasts demonstrated an initial preferential association with cell layers, in comparison to that produced by wild-type fibroblasts. However, the collagen I produced by SPARC-null cells was not efficiently incorporated into detergent-insoluble fractions. Coincident with an initial increase in cell association, greater amounts of total collagen I were present as processed forms in SPARC-null versus wild-type cells. Addition of recombinant SPARC reversed collagen I association with cell layers and decreased the processing of procollagen I in SPARC-null cells. Although collagen fibers formed on the surface of SPARC-null fibroblasts earlier than those on wildtype cells, fibers on SPARC-null fibroblasts did not persist. We conclude that SPARC mediates the association of procollagen I with cells, as well as its processing and incorporation into the extracellular matrix.Matricellular proteins are defined as proteins that are associated with the extracellular matrix (ECM) 2 but are not considered structural components of the ECM, in contrast to classical ECM proteins such as laminin and collagen I (1, 2). SPARC is a prototypic matricellular protein that exhibits counter-adhesive and anti-proliferative activity when added to cultured cells (3). SPARC has been shown to bind to a number of ECM proteins including collagens I, III, and IV (3).Expression of SPARC is elevated during development and decreases upon differentiation in a majority of tissues (4). However, expression of SPARC persists in tissues in which ECM remodeling is ongoing, such as bone and gut epithelia (4). Increased levels of SPARC are detected in response to injury where ECM remodeling is initiated, with fibroses in liver, lungs, and kidney, and in the skin of individuals with scleroderma (5-8). Hence, SPARC expression patterns implicate this protein as an important mediator of collagen I deposition and/or remodeling.The ␣1(I) and ␣2(I) subunits of procollagen I are synthesized with N-and C-propeptides that are enzymatically released by specific proteases to yield processed collagen I (9). Processing of procollagen I to collagen I is essential for correct assembly of collagen fibrils. Spatial and temporal regulation of procollagen processing has been proposed as a potential regulatory event in collagen fibril assembly (9). For example, antibodies against the N-propeptide of collagen I were immunolocalized exclusively to the surface of collagen fibrils that were 20 -40 nm in diameter (10). Retention of the prop...

show abstract

“…SPARC-null mice develop early onset cataracts due in part to aberrant assembly of the lens capsule and disruption of fiber cells (1)(2)(3)(4)(5). SPARC-null mice also show accelerated wound closure (6 -8), enhanced tumor growth (9 -11), increased adipogenesis (12,13), and altered extracellular matrix (ECM) deposition in a variety of tissues.…”

mentioning

confidence: 99%

The Copper Binding Domain of SPARC Mediates Cell Survival in Vitro via Interaction with Integrin β1 and Activation of Integrin-linked Kinase

Weaver¹,

Workman²,

Sage

2008

Journal of Biological Chemistry

Self Cite

100

View full text Add to dashboard Cite

Secreted protein acidic and rich in cysteine (SPARC) is important for the normal growth and maintenance of the murine lens. SPARC-null animals develop cataracts associated with a derangement of the lens capsule basement membrane and alterations in lens fiber morphology. Cellular stress and disregulation of apoptotic pathways within lens epithelial cells (LEC) are linked to cataract formation. To identify molecular targets of SPARC that are linked to this disorder, we stressed wild-type (WT) and SPARC-null LEC by serum deprivation or exposure to tunicamycin. SPARC enhanced signaling by integrin-linked kinase (ILK), a serine/threonine kinase known to enhance cell survival in vitro. In response to stress, an ILK-dependent decrease in apoptosis was observed in WT relative to SPARCnull LEC. Co-immunoprecipitation and cross-linking of cell lysates revealed enhanced levels of a SPARC-integrin ␤1 complex during stress. Competition with monoclonal antibodies and peptides indicated that the copper binding domain of SPARC is required for SPARC-mediated response to stress. Inhibiting the binding and/or activity of ILK, integrin ␤1, or SPARC resulted in increased apoptosis of stressed LEC. We conclude that SPARC protects cells from stress-induced apoptosis in vitro via an interaction with integrin ␤1 heterodimers that enhances ILK activation and pro-survival activity.SPARC (secreted protein acidic and rich in cysteine), 2 a member of the matricellular family of proteins, is important for the development of the murine lens and the maintenance of its transparency. SPARC-null mice develop early onset cataracts due in part to aberrant assembly of the lens capsule and disruption of fiber cells (1-5). SPARC-null mice also show accelerated wound closure (6 -8), enhanced tumor growth (9 -11), increased adipogenesis (12, 13), and altered extracellular matrix (ECM) deposition in a variety of tissues. A secreted glycoprotein, SPARC binds to several integral components of the ECM and exhibits an anti-adhesive function that includes abrogation of focal adhesions and disruption of cell spreading and motility (14,15). SPARC has traditionally been described as a stress-response protein secreted at high levels by cultured cells (16 -18). However, little is known about the role secreted SPARC plays during cellular stress. SPARC has been shown to act as a survival factor in stressed glioma cells (19,20) and to potentiate the invasiveness of certain cancers. Recent work has shown that SPARC regulates cellular assembly of fibronectin by its stimulation of the activity of integrin-linked kinase (ILK) (20, 21). Whereas ILK, by virtue of its interaction with integrin cytoplasmic domains, has been located predominantly on the cytoplasmic side of the plasma membrane, secreted SPARC acts extracellularly at points of integrin-ECM interaction. The juxtaposition of ILK and SPARC across the cell membrane necessitates the involvement of transmembrane proteins for SPARC-mediated alteration of ILK activity. The integrin receptors are logical candidates, as t...

show abstract

Expression of the Matricellular Protein SPARC in Murine Lens: SPARC Is Necessary for the Structural Integrity of the Capsular Basement Membrane

Cited by 37 publications

References 26 publications

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

SPARC Regulates Processing of Procollagen I and Collagen Fibrillogenesis in Dermal Fibroblasts

The Copper Binding Domain of SPARC Mediates Cell Survival in Vitro via Interaction with Integrin β1 and Activation of Integrin-linked Kinase

Contact Info

Product

Resources

About