BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. RESULTS: S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort. CONCLUSIONS: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.

• MeSH
• ANCA-asociované vaskulitidy * komplikace   patologie   MeSH
• atrofie komplikace   patologie   MeSH
• chronická renální insuficience * komplikace   MeSH
• fibróza MeSH
• IgA nefropatie * patologie   MeSH
• kolagen typ VI MeSH
• ledviny patologie   MeSH
• lidé MeSH
• peptidové fragmenty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• kloubní chrupavka patologie   MeSH
• kolagen MeSH
• osteoartróza MeSH

• MeSH
• kolagen fyziologie   genetika   chemie   MeSH
• molekulární biologie MeSH
• Publikační typ
• kongresy MeSH

• MeSH
• kolagen MeSH
• Publikační typ
• kongresy MeSH

• MeSH
• kolagen typ VI genetika   MeSH
• kosterní svaly patologie   MeSH
• laminin genetika   MeSH
• lidé MeSH
• svalová slabost MeSH
• svalové dystrofie * diagnóza   genetika   klasifikace   MeSH
• svalové proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The development of hypoxic pulmonary hypertension is characterized by the structural remodeling of pulmonary arteries. However, the relationship between changes of arterial cells and the extracellular matrix remains unclear. We focused on the evaluation of the non-fibrillar collagen changes in tunica media induced by a four-day exposure to hypoxia and the correlation of these changes with the pulmonary arterial wall structure modifications. We used 20 adult male Wistar rats. The amount and localization of collagen VI, collagen IV, matrix metalloproteinase (MMP) 2, and MMP9 were tested in pulmonary arteries immunohistochemically. Two-dimensional electrophoresis and messenger RNA (mRNA) expression were used for the subsequent comparison of protein changes in arterial tunica media cells (normoxia/hypoxia). Collagen VI was significantly reduced strictly in the tunica media of conduit arteries of hypoxia-exposed rats; however, its mRNA increased. The amount of collagen IV and its mRNA were not altered. We detected a significant increase of MMP9 strictly in the tunica media. In addition, a significantly increased number of MMP9-positive cells surrounded the arteries. MMP2 and the expression of its mRNA were decreased in tunica media. We conclude that the loss of collagen VI is an important step characterizing the remodeling of pulmonary arteries. It could influence the phenotypic status and behavior of smooth muscle cells and modify their proliferation and migration.

• Publikační typ
• časopisecké články MeSH

Bone tissue engineering strategy involves the 3D scaffolds and appropriate cell types promoting the replacement of the damaged area. In this work, we aimed to develop a fast and reliable clinically relevant protocol for engineering viable bone grafts, using cryopreserved adipose tissue-derived mesenchymal stromal cells (MSCs) and composite 3D collagen-nano-hydroxyapatite (nanoHA) scaffolds. Xeno- and DMSO-free cryopreserved MSCs were perfusion-seeded into the biomimetic collagen/nanoHA scaffolds manufactured by cryotropic gelation and their osteoregenerative potential was assessed in vitro and in vivo. Cryopreserved MSCs retained the ability to homogenously repopulate the whole volume of the scaffolds during 7 days of post-thaw culture. Moreover, the scaffold provided a suitable microenvironment for induced osteogenic differentiation of cells, confirmed by alkaline phosphatase activity and mineralization. Implantation of collagen-nanoHA cryogels with cryopreserved MSCs accelerated woven bone tissue formation, maturation of bone trabeculae, and vascularization of femur defects in immunosuppressed rats compared to cell-free collagen-nanoHA scaffolds. The established combination of xeno-free cell culture and cryopreservation techniques together with an appropriate scaffold design and cell repopulation approach accelerated the generation of viable bone grafts.

• MeSH
• buněčná diferenciace MeSH
• kolagen farmakologie   MeSH
• kryogely * MeSH
• kryoprezervace MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• mezenchymální kmenové buňky * metabolismus   MeSH
• osteogeneze MeSH
• proliferace buněk MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• Bethlemova myopatie,
• MeSH
• diferenciální diagnóza MeSH
• kolagen typ VI genetika   MeSH
• lidé MeSH
• myotonická dystrofie * diagnóza   genetika   MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• svalová hypotonie * etiologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• kazuistiky MeSH

Difuzní idiopatická skeletální hyperostóza (DISH) je nezánětlivé onemocnění skeletu charakterizované hyperostózou v oblasti axiálního skeletu i na periferii. Již řadu let je známá jeho souvislost s diabetem II. typu a ostatními metabolickými změnami (porucha metabolismu lipidů), i když souvislost stále není zcela jasná. Zdá se, že důležitou roli v procesu choroby hraje hyperglykemie a insulinoresistence, dále vlivy hormonální, související s růstovým hormonem (GH) a zprostředkování jeho působení prostřednictvím insulin-like growth faktoru (IGF) a jeho binding proteinů (IGFBP2, IGFBP3). Významnou roli v etiologii DISH by mohly hrát i faktory genetické (gen pro kolagen 6 COL6A1), jak je tomu nejspíše u obdobné jednotky – osifikace zadního podélného ligamenta (OPLL).

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory disease characterized by hyperostosis of the axial as well as peripheral skeleton. Its association with diabetes mellitus type II and other metabolic disorders (an impaired lipid profile) has been known for a long time, although the context is not known yet. Hyperglycemia and insulin resistance, then the role of substances that are related to the growth hormones (GF) and mediated by insulin-like growth hormones (IGF) and theirs bindings proteins (IGFBP2, IGFBP3) seem to play an important role in this disease. Genetic factors (collagen type 6 gene COL6A1) could also represent a significant role in the etiology of DISH, such as suggested for a similar entity - ossification of posterior longitudinal ligament (OPLL).

• MeSH
• biologické markery chemie   MeSH
• diabetes mellitus MeSH
• difuzní idiopatická skeletální hyperostóza etiologie   genetika   radiografie   MeSH
• finanční podpora výzkumu jako téma MeSH
• inzulinová rezistence MeSH
• kolagen typ VI genetika   MeSH
• kosti a kostní tkáň metabolismus   MeSH
• lidé MeSH
• osifikace zadního podélného vazu etiologie   genetika   MeSH
• polymorfismus genetický MeSH
• Check Tag
• lidé MeSH

STUDY DESIGN: Genetic screening of collagen 6A1 gene (COL6A1) in patients with diffuse idiopathic skeletal hyperostosis (DISH) recruited in Japan and the Czech Republic. OBJECTIVE: To investigate allelic associations between DISH and nucleotide variants of COL6A1. SUMMARY OF BACKGROUND DATA: DISH is a skeletal hyperostotic disease characterized by ligamentous ossification of the anterolateral side of the spine. Ossification of the posterior longitudinal ligament (OPLL) is a related disorder with DISH, and COL6A1 was identified as a susceptibility gene to OPLL. COL6A1 was examined for susceptibility in DISH patients from Japan and the Czech Republic. METHODS: Seven single nucleotide polymorphisms of COL6A1 were genotyped by direct sequencing. The allele frequencies were compared between 97 Japanese DISH patients and 298 Japanese controls, and between 96 Czech DISH patients and 96 Czech controls by chi2 test. RESULTS: The intron 32 (-29) single nucleotide polymorphisms of COL6A1 was significantly associated with the Japanese DISH patients (chi2 = 9.33; P = 0.0022), but not with the Czech DISH patients. CONCLUSIONS: Because COL6A1 could be a susceptibility to the occurrence of DISH and OPLL in the Japanese population, we consider that COL6A1 could be responsible for the hyperostotic state, leading to ectopic bone formation in the spinal ligament.

• MeSH
• alely MeSH
• Asijci * genetika   MeSH
• běloši genetika   MeSH
• difuzní idiopatická skeletální hyperostóza * genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• genotyp MeSH
• introny MeSH
• jednonukleotidový polymorfismus MeSH
• kolagen typ VI * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osifikace zadního podélného vazu * genetika   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH