Publications (84) View all
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Article: Abnormal Corneal Endothelial Maturation in Collagen XII and XIV Null Mice.
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ABSTRACT: Purpose. Maturation of the endothelium and the adjacent matrix was characterized in wild type mice. The influence of FACIT collagen XII and XIV deficiency on the morphology, maturation and function of the corneal endothelium was examined. Methods. Analysis of the endothelium and Descemet's membrane (DM) was performed using transmission electron microscopy at postnatal day (P) P4, P14 and P30 in wild type (WT), Col12a1-/-, Col14a1-/- and Col12a1-/-/Col14a1-/- mice. Endothelial junctions were analyzed using ZO-1. The presence of endothelial - stromal communications was evaluated with phalloidin staining as well as electron microscopy. Finally, corneal thickness was assessed. Results. A thin DM, clefts between endothelial cells and DM and large 'vacuole-like' structures were present in the endothelial cells of WT mice at P4 and not noted at P30. The endothelia of Col12a1-/-, Col14a1-/- and compound Col12a1-/-/Col14a1-/- in the P30 cornea maintained the "vacuole-like' structures seen at P4. A mature endothelial junction pattern was delayed in the null corneas. Expression of ZO-1 in WT endothelia at P14 was diffuse and localized to the basolateral and apical cell membrane. At P30, staining was localized to intercellular junctions. ZO-1 reactivity was patchy in Col12a1-/-, Col14a1-/- and compound Col12a1-/-/Col14a1-/- corneas at P14 and P30. Stromal thickness was increased in P30 null corneas. Endothelial cell processes were demonstrated penetrating the DM and into the underlying stroma, throughout the entire endothelial layer in the P4 cornea. Conclusions. Collagen XII and XIV null mice demonstrate delayed endothelial maturation. The structural alterations suggest functional changes including permeability and corneal thickness. Endothelial-stromal interactions suggest a pathway for signal transduction.Investigative ophthalmology & visual science 04/2013; · 3.43 Impact Factor -
Article: Zebrafish collagen XIV is transiently expressed in epithelia and is required for proper function of certain basement membranes.
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ABSTRACT: We found that zebrafish has two differentially expressed col14a1 paralogs. col14a1a expression peaked between 18-somite stage and 24 hpf, whereas col14a1b was first expressed at 32 hpf. To uncover functions of collagen XIV (COLXIV) during early embryogenesis, we focused our study on col14a1a. We characterized the α1 (XIV-A) chain as a collagenase-sensitive 200 kDa protein that formed dimer that could be reduced at high pH. As observed for the transcript, COLXIV-A protein expression peaked between 24 and 48 hpf. Using anti-sense probes and polyclonal antibodies, we show that col14a1a and its protein product COLXIV-A, are transiently expressed in several epithelia, including epithelia undergoing shape changes, such as the fin folds. In contrast, anti-COLXII antibodies stained only connective tissues. COLXIV-A was also detected in the BM, where it co-localized with COLXII. At later developmental stages, COLXIV-A was not expressed in epithelia anymore, but persisted in the BM. Morpholino (MO) knockdown of COLXIV-A provoked a skin detachment phenotype. Electron microscopy analysis revealed that MO-injected embryos lacked a lamina densa and lamina lucida at 24 hpf, and BM defects, such as gaps in the adepidermal granules, were still detected at 48 hpf. These BM defects were accompanied by a rupture of the dermis, and detachment of the epidermis. Taken together, these data suggest an unexpected role of COLXIV-A in undifferentiated epithelia and in the formation of embryonic basement membranes.Journal of Biological Chemistry 01/2013; · 4.77 Impact Factor -
Dataset: 1-s2.0-S0378111901003638-main
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Article: Collagen XIV is important for growth and structural integrity of the myocardium.
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ABSTRACT: Collagen XIV is a fibril-associated collagen with an interrupted triple helix (FACIT). Previous studies have shown that this collagen type regulates early stages of fibrillogenesis in connective tissues of high mechanical demand. Mice null for Collagen XIV are viable, however formation of the interstitial collagen network is defective in tendons and skin leading to reduced biomechanical function. The assembly of a tightly regulated collagen network is also required in the heart, not only for structural support but also for controlling cellular processes. Collagen XIV is highly expressed in the embryonic heart, notably within the cardiac interstitium of the developing myocardium, however its role has not been elucidated. To test this, we examined cardiac phenotypes in embryonic and adult mice devoid of Collagen XIV. From as early as E11.5, Col14a1(-/-) mice exhibit significant perturbations in mRNA levels of many other collagen types and remodeling enzymes (MMPs, TIMPs) within the ventricular myocardium. By post natal stages, collagen fibril organization is in disarray and the adult heart displays defects in ventricular morphogenesis. In addition to the extracellular matrix, Col14a1(-/-) mice exhibit increased cardiomyocyte proliferation at post natal, but not E11.5 stages, leading to increased cell number, yet cell size is decreased by 3months of age. In contrast to myocytes, the number of cardiac fibroblasts is reduced after birth associated with increased apoptosis. As a result of these molecular and cellular changes during embryonic development and post natal maturation, cardiac function is diminished in Col14a1(-/-) mice from 3months of age; associated with dilation in the absence of hypertrophy, and reduced ejection fraction. Further, Col14a1 deficiency leads to a greater increase in left ventricular wall thickening in response to pathological pressure overload compared to wild type animals. Collectively, these studies identify a new role for type XIV collagen in the formation of the cardiac interstitium during embryonic development, and highlight the importance of the collagen network for myocardial cell survival, and function of the working myocardium after birth.Journal of Molecular and Cellular Cardiology 08/2012; 53(5):626-38. · 5.17 Impact Factor -
Article: Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.
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ABSTRACT: The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone.Journal of Biological Chemistry 05/2012; 287(27):22549-59. · 4.77 Impact Factor
