Gliomagenesis induces profound changes in the composition of the extracellular matrix (ECM) of the brain. In this study, we identified a cellular population responsible for the increased deposition of collagen I and fibronectin in glioblastoma. Elevated levels of the fibrillar proteins collagen I and fibronectin were associated with the expression of fibroblast activation protein (FAP), which is predominantly found in pericyte-like cells in glioblastoma. FAP+ pericyte-like cells were present in regions rich in collagen I and fibronectin in biopsy material and produced substantially more collagen I and fibronectin in vitro compared to other cell types found in the GBM microenvironment. Using mass spectrometry, we demonstrated that 3D matrices produced by FAP+ pericyte-like cells are rich in collagen I and fibronectin and contain several basement membrane proteins. This expression pattern differed markedly from glioma cells. Finally, we have shown that ECM produced by FAP+ pericyte-like cells enhances the migration of glioma cells including glioma stem-like cells, promotes their adhesion, and activates focal adhesion kinase (FAK) signaling. Taken together, our findings establish FAP+ pericyte-like cells as crucial producers of a complex ECM rich in collagen I and fibronectin, facilitating the dissemination of glioma cells through FAK activation.

• Klíčová slova
• collagen type I, extracellular matrix proteins, fibronectin, glioblastoma, pericytes, proteomics,
• MeSH
• endopeptidasy MeSH
• extracelulární matrix * metabolismus   patologie   MeSH
• fibronektiny * metabolismus   MeSH
• glioblastom patologie   metabolismus   MeSH
• gliom * patologie   metabolismus   MeSH
• kolagen typu I metabolismus   MeSH
• lidé MeSH
• membránové proteiny metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí fyziologie   MeSH
• nádory mozku * patologie   metabolismus   MeSH
• pericyty * metabolismus   patologie   MeSH
• pohyb buněk fyziologie   MeSH
• serinové endopeptidasy metabolismus   MeSH
• želatinasy metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endopeptidasy MeSH
• fibroblast activation protein alpha MeSH Prohlížeč
• fibronektiny * MeSH
• kolagen typu I MeSH
• membránové proteiny MeSH
• serinové endopeptidasy MeSH
• želatinasy MeSH

Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.

• Klíčová slova
• Fibrosis, Gastroenterology, Inflammation, Inflammatory bowel disease, Monocytes,
• MeSH
• Crohnova nemoc * metabolismus   patologie   imunologie   MeSH
• dospělí MeSH
• endopeptidasy metabolismus   genetika   MeSH
• extracelulární matrix metabolismus   patologie   MeSH
• fibroblasty * metabolismus   patologie   MeSH
• fibróza * MeSH
• ileum patologie   metabolismus   imunologie   MeSH
• jaderné proteiny metabolismus   genetika   MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• monocyty * metabolismus   patologie   imunologie   MeSH
• myši MeSH
• receptory buněčného povrchu metabolismus   genetika   MeSH
• transkripční faktor Twist * metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endopeptidasy MeSH
• jaderné proteiny MeSH
• receptory buněčného povrchu MeSH
• transkripční faktor Twist * MeSH
• TWIST1 protein, human MeSH Prohlížeč

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.

• MeSH
• apoptóza * MeSH
• chondrocyty * metabolismus   patologie   MeSH
• dítě MeSH
• extracelulární matrix * metabolismus   patologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mikro RNA * metabolismus   genetika   MeSH
• mladiství MeSH
• osteoartróza * metabolismus   patologie   genetika   MeSH
• protein PEBP2alfaA * metabolismus   genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• protein PEBP2alfaA * MeSH
• RUNX2 protein, human MeSH Prohlížeč

Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn. Lamina I PNNs selectively enwrap spinoparabrachial projection neurons, which integrate nociceptive information in the spinal cord and convey it to supraspinal brain regions to induce pain sensation. Degradation of PNNs by microglia enhances the activity of projection neurons and induces pain-related behaviors. Thus, nerve injury-induced degradation of PNNs is a mechanism by which microglia selectively augment the output of spinal nociceptive circuits and cause pain hypersensitivity.

• MeSH
• bolest * patologie   patofyziologie   MeSH
• extracelulární matrix patologie   MeSH
• hyperalgezie * etiologie   patologie   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• mikroglie * patologie   MeSH
• poranění periferního nervu * komplikace   patologie   MeSH
• potkani Sprague-Dawley MeSH
• zadní rohy míšní * patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

• MeSH
• buněčná diferenciace * genetika   MeSH
• celogenomová asociační studie MeSH
• extracelulární matrix * metabolismus   patologie   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické lokusy * MeSH
• hodnocení rizik MeSH
• jednonukleotidový polymorfismus * MeSH
• keratokonus * diagnóza   etnologie   genetika   metabolismus   MeSH
• kolagen * metabolismus   MeSH
• lidé MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Austrálie epidemiologie   MeSH
• Evropa epidemiologie   MeSH
• Názvy látek
• kolagen * MeSH

Cells have developed a unique set of molecular mechanisms that allows them to probe mechanical properties of the surrounding environment. These systems are based on deformable primary mechanosensors coupled to tension transmitting proteins and enzymes generating biochemical signals. This modular setup enables to transform a mechanical load into more versatile biochemical information. Src kinase appears to be one of the central components of the mechanotransduction network mediating force-induced signalling across multiple cellular contexts. In tight cooperation with primary sensors and the cytoskeleton, Src functions as an effector molecule necessary for transformation of mechanical stimuli into biochemical outputs executing cellular response and adaptation to mechanical cues.

• Klíčová slova
• Cytoskeleton, Integrins, Mechanosensing, Src, YAP, p130Cas,
• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• buněčný převod mechanických signálů genetika   MeSH
• cytoskelet metabolismus   patologie   ultrastruktura   MeSH
• extracelulární matrix metabolismus   patologie   ultrastruktura   MeSH
• integriny genetika   metabolismus   MeSH
• lidé MeSH
• mechanický stres MeSH
• nádory genetika   metabolismus   patologie   MeSH
• protein-serin-threoninkinasy genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• signální dráha Hippo MeSH
• signální proteiny YAP MeSH
• skupina kinas odvozených od src-genu genetika   metabolismus   MeSH
• substrátový protein asociovaný s Crk genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• tyrosinfosfatasy receptorového typu, třída 4 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• BCAR1 protein, human MeSH Prohlížeč
• integriny MeSH
• protein-serin-threoninkinasy MeSH
• PTPRA protein, human MeSH Prohlížeč
• signální proteiny YAP MeSH
• skupina kinas odvozených od src-genu MeSH
• substrátový protein asociovaný s Crk MeSH
• transkripční faktory MeSH
• tyrosinfosfatasy receptorového typu, třída 4 MeSH
• YAP1 protein, human MeSH Prohlížeč

Excessive connective tissue accumulation, a hallmark of hypertrophic scaring, results in progressive deterioration of the structure and function of organs. It can also be seen during tumor growth and other fibroproliferative disorders. These processes result from a wide spectrum of cross-talks between mesenchymal, epithelial and inflammatory/immune cells that have not yet been fully understood. In the present review, we aimed to describe the molecular features of fibroblasts and their interactions with immune and epithelial cells and extracellular matrix. We also compared different types of fibroblasts and their roles in skin repair and regeneration following burn injury. In summary, here we briefly review molecular changes underlying hypertrophic scarring following burns throughout all basic wound healing stages, i.e. during inflammation, proliferation and maturation.

• Klíčová slova
• burn, cell interaction, pathological scar, skin, stem cell, wound healing,
• MeSH
• epitelové buňky metabolismus   patologie   MeSH
• extracelulární matrix metabolismus   patologie   MeSH
• fibroblasty metabolismus   patologie   MeSH
• hojení ran genetika   MeSH
• jizva hypertrofická genetika   imunologie   patologie   MeSH
• lidé MeSH
• popálení genetika   patologie   MeSH
• proliferace buněk genetika   MeSH
• zánět genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Within the tumour microenvironment, tumour cells are exposed to different mechanical stimuli such as compression stress, cell-cell and cell-extracellular matrix traction forces, interstitial fluid pressure, and shear stress. Cells actively sense and process this information by the mechanism of mechanotransduction to make decisions about their growth, motility, and differentiation. Indeed, the mechanical properties of the tumour microenvironment can deeply influence the behaviour of cancer cells and promote cancerogenesis. During tumour progression, desmoplasia arises and a positive feedback loop between the stiffening extracellular matrix and the properties enabling tumour expansion is established. Tumour cells can use mechanic stimuli to promote proliferation, increase their migratory and invasive potential, and induce therapeutic resistance. Mechanobio-logy is a progressive multidisciplinary field which studies how mechanical forces influence the behaviour of cells or tissues and may provide some interesting targets for cancer therapy. PURPOSE: In this review, we discuss the mechanical properties of cancer cells and describe the tumour promoting effect of the transformed extracellular matrix. We propose that the differences in the mechanobio-logy of cells and extracellular matrix are significant enough to facilitate tumorigenesis and may provide interesting targets for cancer therapy.

• Klíčová slova
• cancer, extracellular matrix, malignancy, mechanobio­logy, mechanotransduction, shear stress, therapy resistence,
• MeSH
• biofyzika * MeSH
• buněčný převod mechanických signálů * MeSH
• extracelulární matrix patologie   MeSH
• lidé MeSH
• nádorová transformace buněk * MeSH
• nádorové mikroprostředí * MeSH
• nádory patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

3D cell culture methods have been an integral part of and an essential tool for mammary gland and breast cancer research for half a century. In fact, mammary gland researchers, who discovered and deciphered the instructive role of extracellular matrix (ECM) in mammary epithelial cell functional differentiation and morphogenesis, were the pioneers of the 3D cell culture techniques, including organoid cultures. The last decade has brought a tremendous increase in the 3D cell culture techniques, including modifications and innovations of the existing techniques, novel biomaterials and matrices, new technological approaches, and increase in 3D culture complexity, accompanied by several redefinitions of the terms "3D cell culture" and "organoid". In this review, we provide an overview of the 3D cell culture and organoid techniques used in mammary gland biology and breast cancer research. We discuss their advantages, shortcomings and current challenges, highlight the recent progress in reconstructing the complex mammary gland microenvironment in vitro and ex vivo, and identify the missing 3D cell cultures, urgently needed to aid our understanding of mammary gland development, function, physiology, and disease, including breast cancer.

• Klíčová slova
• 3D cell culture, Breast, Co-culture, Extracellular matrix, Imaging, Microenvironment, Organoid, Screening, Stromal cells,
• MeSH
• buněčná diferenciace MeSH
• buněčné kultury přístrojové vybavení   MeSH
• buněčné sféroidy patologie   MeSH
• epitelové buňky patologie   MeSH
• extracelulární matrix patologie   MeSH
• kokultivační techniky metody   MeSH
• lidé MeSH
• mléčné žlázy lidské cytologie   patologie   MeSH
• mléčné žlázy zvířat cytologie   patologie   MeSH
• modely u zvířat MeSH
• myši MeSH
• nádory prsu patologie   MeSH
• organoidy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Hapln4 is a link protein which stabilizes the binding between lecticans and hyaluronan in perineuronal nets (PNNs) in specific brain regions, including the medial nucleus of the trapezoid body (MNTB). The aim of this study was: (1) to reveal possible age-related alterations in the extracellular matrix composition in the MNTB and inferior colliculus, which was devoid of Hapln4 and served as a negative control, (2) to determine the impact of the Hapln4 deletion on the values of the ECS diffusion parameters in young and aged animals and (3) to verify that PNNs moderate age-related changes in the ECS diffusion, and that Hapln4-brevican complex is indispensable for the correct protective function of the PNNs. To achieve this, we evaluated the ECS diffusion parameters using the real-time iontophoretic method in the selected region in young adult (3 to 6-months-old) and aged (12 to 18-months-old) wild type and Hapln4 knock-out (KO) mice. The results were correlated with an immunohistochemical analysis of the ECM composition and astrocyte morphology. We report that the ECM composition is altered in the aged MNTB and aging is a critical point, revealing the effect of Hapln4 deficiency on the ECS diffusion. All of our findings support the hypothesis that the ECM changes in the MNTB of aged KO animals affect the ECS parameters indirectly, via morphological changes of astrocytes, which are in direct contact with synapses and can be influenced by the ongoing synaptic transmission altered by shifts in the ECM composition.

• Klíčová slova
• Aging, Diffusion, Extracellular matrix, Extracellular space, Hapln4,
• MeSH
• corpus trapezoideum metabolismus   patologie   MeSH
• difuze * MeSH
• extracelulární matrix - proteiny nedostatek   MeSH
• extracelulární matrix metabolismus   patologie   MeSH
• extracelulární prostor metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• nedostatek proteinů metabolismus   patologie   MeSH
• orgánové kultury - kultivační techniky MeSH
• periferní nervy metabolismus   patologie   MeSH
• proteiny nervové tkáně nedostatek   MeSH
• sluchová dráha metabolismus   patologie   MeSH
• stárnutí metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• extracelulární matrix - proteiny MeSH
• Hapln4 protein, mouse MeSH Prohlížeč
• proteiny nervové tkáně MeSH