Collagen fibril assembly by corneal fibroblasts in three-dimensional collagen gel cultures: Small-diameter heterotypic fibrils are deposited in the absence of keratan sulfate proteoglycan

Doane, Kathleen J.; Babiarz, Joanne; Fitch, John M.; Linsenmayer, Thomas F.; Birk, David E.

doi:10.1016/0014-4827(92)90410-a

Cited by 44 publications

(34 citation statements)

References 39 publications

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“…In the secondary corneal stroma, the small diameters of the collagen fibrils are thought to result from the incorporation of a relatively large proportion of type V collagen into heterotypic type I + V fibrils (Doane et al, 1992;Birk et al, 1990); control of fibril diameter is 43 thought to be exerted by the presence of a large aminoterminal globular domain of type V (Linsenmayer et al, 1993) that serves to inhibit lateral growth of the fibril. It is reasonable to assume that fibril diameter in the primary stroma is controlled in a similar fashion, but by a different collagen type (see below): these fibrils contain, along with type I collagen, type I1 collagen instead of type V.…”

Section: Introductionmentioning

confidence: 99%

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction

Fitch

Gordon

Gibney

et al. 1995

Developmental Dynamics

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The genes for the al(IX), al(II), and a2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for al(1X) and &?(I)] or alternative splicing [for cyl(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of al(1X) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of al(1X) was from the downstream promotor (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type I1 gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type I1 collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, 111, and V. For type I, the "bone/tendon" mRNA isoform of the cy2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and 11, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 112 day cartilage, long IX was expressed predominantly along with the IIB form of al(1I). The downstream transcript of the a2(I) gene (Icart) was found at high levels only in cartilage.

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Section: Introductionmentioning

confidence: 99%

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction

Fitch

Gordon

Gibney

et al. 1995

Developmental Dynamics

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“…The mechanisms that govern the assembly of different levels of stromal architecture are not well understood; however, proteoglycan-collagen and collagen-collagen interactions have been implicated. It has been suggested that the stoichiometry and interaction of different collagen types play an important role in modulating collagen fibril diameter (1,(3)(4)(5). The proteoglycans in the stroma are members of the small leucine-rich proteoglycan (SLRP) 1 gene family and are thought to regulate collagenous matrix assembly in connective tissue because of their bifunctional character: the protein moiety that binds collagen fibrils and the highly charged hydrophilic glycosaminoglycans that regulate interfibrillar spacing (1, 2, 6 -11).…”

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confidence: 99%

Keratocan-deficient Mice Display Alterations in Corneal Structure

Liu

Birk

Hassell

et al. 2003

Journal of Biological Chemistry

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164

137

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Keratocan (Kera) is a cornea-specific keratan sulfate proteoglycan (KSPG) in the adult vertebrate eye. It belongs to the small leucine-rich proteoglycan (SLRP) gene family and is one of the major components of extracellular KSPG in the vertebrate corneal stroma. The Kera gene is expressed in ocular surface tissues including cornea and eyelids during morphogenesis. Corneal KSPGs play a pivotal role in matrix assembly, which is accountable for corneal transparency. In humans, mutations of the KERA gene are associated with cornea plana (CNA2) that manifests decreases in vision acuity due to the flattened forward convex curvature of cornea. To investigate the biological role of the Kera gene and to establish an animal model for corneal plana, we generated Kera knockout mice via gene targeting. Northern and Western blotting and immunohistochemical analysis showed that no Kera mRNA or keratocan protein was detected in the Kera ؊/؊ cornea. The expression levels of other SLRP members including lumican, decorin, and fibromodulin were not altered in the Kera ؊/؊ cornea as compared with that of the wild-type littermates. Mice lacking keratocan have normal corneal transparency at the age of 12 months. However, they have a thinner corneal stroma and a narrower cornea-iris angle of the anterior segment in comparison to the wild-type littermates. As demonstrated by transmission electron microscopy, Kera ؊/؊ mice have larger stromal fibril diameters and less organized packing of collagen fibrils in stroma than those of wild type. Taken together, our results showed that ablation of the Kera gene resulted in subtle structural alterations of collagenous matrix and did not perturb the expression of other SLRPs in cornea. Keratocan thus plays a unique role in maintaining the appropriate corneal shape to ensure normal vision.The vertebrate cornea is a tough and transparent tissue that provides greater than 60% of refractive power to the incoming light to cast a focused image on retina. To exact its proper functions, the cornea has to maintain transparent, appropriate curvature for refraction and toughness for protection. Genetic and epigenetic factors that cause the change of corneal curvature, reduction of transparency, and weakness in structure can lead to the impairment of visual acuity.The corneal stroma consists of uniformly small collagen fibrils with an average diameter of 25 nm that are arranged in orthogonal lamellae. Stromal keratocytes are responsible for the formation and maintenance of a unique collagenous matrix that is essential for proper corneal curvature and transparency (1, 2). The mechanisms that govern the assembly of different levels of stromal architecture are not well understood; however, proteoglycan-collagen and collagen-collagen interactions have been implicated. It has been suggested that the stoichiometry and interaction of different collagen types play an important role in modulating collagen fibril diameter (1, 3-5). The proteoglycans in the stroma are members of the small leucine-rich proteoglycan (SLR...

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“…It has been proposed that a function for these PGs on the collagen fibril surface may be to determine and modify the surface properties and, therefore, interactions with other matrix macromolecules as suggested from studies in cartilage [28]. Our demonstration of an increase in fibromodulin mRNA during the later stages of matrix assembly suggests a role for this PG in the organization of fibrils into fibres and tissue-specific matrices [12,29].…”

Section: Discussionmentioning

confidence: 62%

Differential expression of fibromodulin mRNA associated with tendon fibril growth: isolation and characterization of a chicken fibromodulin cDNA

Nurminskaya

Birk

1996

Biochemical Journal

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A 450 bp cDNA fragment similar to that encoding bovine fibromodulin was isolated using a screening procedure to isolate genes differentially expressed between the pre- and post-growth phases of fibril growth in the developing chicken embryo metatarsal tendon. Using this fragment, a 2.4 kb cDNA clone for chicken fibromodulin was isolated from a λZAP library, and the 5´ rapid amplification of cDNA ends technique was employed to clone the 5´ end of the fibromodulin cDNA. The full-length cDNA contained an open reading frame coding for a 380-amino-acid protein. There was ∼80% similarity with human, rat and bovine fibromodulins, which confirmed its identity as fibromodulin. Structural features of the deduced sequence include an 18-amino-acid signal peptide, cysteine residues in conserved positions in the N- and C-terminal regions, and a central leucine-rich domain containing eleven repeats of the sequence LXXLXLXXNXL/I. Features unique to chicken fibromodulin include an additional glycosylation site as well as a decreased number of tyrosine residues that could be sulphated, and therefore potential changes in the charge of the molecule. In addition, there was little similarity among the untranslated regions. When compared with chicken decorin and lumican, fibromodulin showed greater similarity to the other keratan sulphate-containing proteoglycan, lumican. Northern blot analysis revealed a 6–8-fold increase in the fibromodulin mRNA level from day 14 to day 19 of development. In the chicken tendon, collagen fibril growth is a process characterized by a precipitous increase in length during a short developmental period. The necessary changes would require the expression of different genes regulating fibril formation and growth, and interactions between fibromodulin and collagen fibrils may participate in the regulation of collagen fibril growth and matrix assembly.

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Collagen fibril assembly by corneal fibroblasts in three-dimensional collagen gel cultures: Small-diameter heterotypic fibrils are deposited in the absence of keratan sulfate proteoglycan

Cited by 44 publications

References 39 publications

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction

Keratocan-deficient Mice Display Alterations in Corneal Structure

Differential expression of fibromodulin mRNA associated with tendon fibril growth: isolation and characterization of a chicken fibromodulin cDNA

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