| 1. |
- Halasz, Krisztina, et al.
(författare)
-
COMP acts as a catalyst in collagen fibrillogenesis
- 2007
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 282:43, s. 31166-31173
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously reported that COMP (cartilage oligomeric matrix protein) is prominent in cartilage but is also present in tendon and binds to collagens I and II with high affinity. Here we show that COMP influences the fibril formation of these collagens. Fibril formation in the presence of pentameric COMP was much faster, and the amount of collagen in fibrillar form was markedly increased. Monomeric COMP, lacking the N-terminal coiled-coil linker domain, decelerated fibrillogenesis. The data show that stimulation of collagen fibrillogenesis depends on the pentameric nature of COMP and not only on collagen binding. COMP interacts primarily with free collagen I and II molecules, bringing several molecules to close proximity, apparently promoting further assembly. These assemblies further join in discrete steps to a narrow distribution of completed fibril diameters of 149 +/- 16 nm with a banding pattern of 67 nm. COMP is not found associated with the mature fibril and dissociates from the collagen molecules or their early assemblies. However, a few COMP molecules are found bound to more loosely associated molecules at the tip/end of the growing fibril. Thus, COMP appears to catalyze the fibril formation by promoting early association of collagen molecules leading to increased rate of fibrillogenesis and more distinct organization of the fibrils.
|
|
| 2. |
- Hesselstrand, Roger, et al.
(författare)
-
COMP a candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker
- 2008
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 67:9, s. 1242-1248
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: COMP primarily found in cartilage is thought to be an important regulator of assembly and maintenance of the fibrillar collagen I and II networks. Recently COMP was shown to be produced by skin fibroblasts from patients with systemic sclerosis (SSc, scleroderma). The purpose of this study was to examine whether COMP is released from skin to serum in SSc patients, and may serve as indicator of activity of skin involvement. METHODS: Serum COMP levels were measured by enzyme linked immunosorbent assay in patients with SSc whose skin involvement was assessed with the modified Rodnan skin score (mRss) and high frequency ultrasound. The presence of COMP in skin biopsies was assessed by Western blot using a monoclonal antibody to the very C-terminal end of human COMP. RESULTS: Serum COMP correlated to skin involvement as measured by the mRss (n=70; rS=0.60; p<0.001), to skin thickness measured by ultrasound (n=88; rS=0.55; p<0.001) and inversely to skin echogenicity measured by ultrasound (n=88; rS=-0.40; p<0.001). In 70 patients followed longitudinally there was a correlation between changes in serum COMP (n=307) and changes in mRss (rS=0.35; p=0.008). In individual patients monitored with repeated measurements, serum COMP changes closely paralleled changes in mRss. A C-terminal COMP fragment, with an apparent Mr 56 kDa, was identified in SSc skin biopsies, while no COMP-reactivity was detected in normal skin. CONCLUSION: The high turnover of COMP in SSc skin suggests a pathophysiologic role. Serum COMP shows promise as a new biomarker in SSc.
|
|
| 3. |
- Lidén, Åsa, et al.
(författare)
-
A secreted collagen- and fibronectin-binding streptococcal protein modulates cell-mediated collagen gel contraction and interstitial fluid pressure
- 2008
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:3, s. 1234-1242
-
Tidskriftsartikel (refereegranskat)abstract
- Fibroblast-mediated collagen gel contraction depends on collagen-binding beta1 integrins. Perturbation of these integrins reveals an alternative contraction process that is integrin alphaVbeta3-dependent and platelet-derived growth factor (PDGF) BB-stimulated. Connective tissue cells actively control interstitial fluid pressure (IFP), and inflammation-induced lowering of IFP provides a driving force for edema formation. PDGF-BB normalizes a lowered IFP by an alphaVbeta3-dependent process. A potential modulation of IFP by extracellular matrix-binding bacterial proteins has previously not been addressed. The fibronectin (FN)-binding protein FNE is specifically secreted by the highly virulent Streptococcus equi subspecies equi. FNE bound FN and native collagen type I with K(d) values of approximately 20 and approximately 50 nm determined by solid-phase binding assays. Rotary shadowing revealed a single FNE binding site located at on average 122 nm from the C terminus of procollagen type I. FNE induced alphaVbeta3-mediated contraction by C2C12 cells in a concentration-dependent manner having a maximal effect at approximately 100 nm. This activity of FNE required cellular FN, and FNE acted synergistically to added plasma FN or PDGF-BB. FNE enhanced binding of soluble FN to immobilized collagen, and conversely the binding of collagen to immobilized FN. Marked bell-shaped concentration dependences for these interactions suggest that FNE forms a bridge between FN and collagen. Finally, FNE normalized dermal IFP lowered by anaphylaxis. Our data suggest that secreted FNE normalized lowering of IFP by stimulating connective tissue cell contraction.
|
|
