Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.
- MeSH
- autoimunita * MeSH
- hojení ran * imunologie MeSH
- interleukin-6 * metabolismus imunologie MeSH
- lidé MeSH
- nádorové mikroprostředí * imunologie MeSH
- nádory * imunologie metabolismus patologie MeSH
- stárnutí * imunologie MeSH
- zánět * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‐associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‐expression of keratins‐8/‐14 in the EM‐G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‐8, ‐14, ‐18, ‐19) and epithelial‐mesenchymal transition‐associated markers (SLUG, SNAIL, ZEB1, E‐/N‐cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‐A and MFGE8 attenuated the modulatory effect of CAFs on EM‐G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‐G3 cells in vitro. CAFs of different origins support the pro‐inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.
- MeSH
- antigeny povrchové MeSH
- fibroblasty asociované s nádorem * metabolismus MeSH
- fibroblasty metabolismus MeSH
- keratiny genetika metabolismus MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- MFC-7 buňky MeSH
- mléčné bílkoviny genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí genetika MeSH
- nádory prsu * farmakoterapie genetika metabolismus MeSH
- prognóza MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Termický úraz je jedno z najzávažnejších zranení v traumatológii. Popáleniny nesú so sebou veľa rizík, z ktorých najzávažnejšie je ohrozenie života a v neposlednom rade trvalé následky. Hlavnou klasifikáciou popálenín je rozdelenie na dve skupiny podľa hĺbky poranenia. Hĺbka určuje aj následný spôsob ošetrenia popálenej plochy. Povrchové popáleniny ošetrujeme konzervatívnym postupom, hlboké popáleniny si vyžadujú často chirurgický prístup. Špecifickou skupinou sú detskí pacienti. Liečba popálenín v Českej republike pozostáva zo siete tvorenej tromi špecializovanými popáleninovými centrami (Praha, Brno, Ostrava), ktoré hospitalizujú pacientov s najzávažnejšími termickými úrazmi z celej ČR i zahraničia. Menej závažné prípady popálených pacientov môžu byť ošetrované cestou spádových chirurgických ambulancií.
Thermal injuries belong to the most severe ones in traumatology. Burn injuries pose numerous risks, the most critical ones are life-threatening and potentially resulting in permanent damage. The main classification of burn injuries is based on the depth of the injury, which determines the appropriate treatment method. Superficial burns are typically treated conservatively, while deep burns often require surgical intervention. Children represent a very specific group of burn patients. In the Czech Republic, burn injury treatment is centralized in three specialized burn centres (Prague, Brno, Ostrava) that hospitalize patients with the most severe thermal injuries from the whole country and abroad. Less serious thermal burns can be treated at local surgery departments.
Termický úraz je jedno z najzávažnejších zranení v traumatológii. Popáleniny nesú so sebou veľa rizík, z ktorých najzávažnejšie je ohrozenie života a v neposlednom rade trvalé následky. Hlavnou klasifikáciou popálenín je rozdelenie na dve skupiny podľa hĺbky poranenia. Hĺbka určuje aj následný spôsob ošetrenia popálenej plochy. Povrchové popáleniny ošetrujeme konzervatívnym postupom, hlboké popáleniny si vyžadujú často chirurgický prístup. Špecifickou skupinou sú detskí pacienti. Liečba popálenín v Českej republike pozostáva zo siete tvorenej tromi špecializovanými popáleninovými centrami (Praha, Brno, Ostrava), ktoré hospitalizujú pacientov s najzávažnejšími termickými úrazmi z celej ČR i zahraničia. Menej závažné prípady popálených pacientov môžu byť ošetrované cestou spádových chirurgických ambulancií.
Thermal injuries belong to the most severe ones in traumatology. Burn injuries pose numerous risks, the most critical ones are life-threatening and potentially resulting in permanent damage. The main classification of burn injuries is based on the depth of the injury, which determines the appropriate treatment method. Superficial burns are typically treated conservatively, while deep burns often require surgical intervention. Children represent a very specific group of burn patients. In the Czech Republic, burn injury treatment is centralized in three specialized burn centres (Prague, Brno, Ostrava) that hospitalize patients with the most severe thermal injuries from the whole country and abroad. Less serious thermal burns can be treated at local surgery departments.
Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.
- MeSH
- hojení ran MeSH
- jizva etiologie prevence a kontrola chirurgie MeSH
- kůže patologie MeSH
- lidé MeSH
- popálení * chirurgie patologie MeSH
- transplantace kůže metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Identification of therapeutic targets for treating fibrotic diseases and cancer remains challenging. Our study aimed to investigate the effects of TGF-β1 and TGF-β3 on myofibroblast differentiation and extracellular matrix deposition in different types of fibroblasts, including normal/dermal, cancer-associated, and scar-derived fibroblasts. When comparing the phenotype and signaling pathways activation we observed extreme heterogeneity of studied markers across different fibroblast populations, even within those isolated from the same tissue. Specifically, the presence of myofibroblast and deposition of extracellular matrix were dependent on the origin of the fibroblasts and the type of treatment they received (TGF-β1 vs. TGF-β3). In parallel, we detected activation of canonical signaling (pSMAD2/3) across all studied fibroblasts, albeit to various extents. Treatment with TGF-β1 and TGF-β3 resulted in the activation of canonical and several non-canonical pathways, including AKT, ERK, and ROCK. Among studied cells, cancer-associated fibroblasts displayed the most heterogenic response to TGF-β1/3 treatments. In general, TGF-β1 demonstrated a more potent activation of signaling pathways compared to TGF-β3, whereas TGF-β3 exhibited rather an inhibitory effect in keloid- and hypertrophic scar-derived fibroblasts suggesting its clinical potential for scar treatment. In summary, our study has implications for comprehending the role of TGF-β signaling in fibroblast biology, fibrotic diseases, and cancer. Future research should focus on unraveling the mechanisms beyond differential fibroblast responses to TGF-β isomers considering inherent fibroblast heterogeneity.
- MeSH
- fibroblasty metabolismus MeSH
- hojení ran MeSH
- jizva hypertrofická * metabolismus patologie MeSH
- karcinogeneze metabolismus patologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorová transformace buněk metabolismus MeSH
- protein - isoformy metabolismus MeSH
- transformující růstový faktor beta metabolismus MeSH
- transformující růstový faktor beta1 * farmakologie metabolismus MeSH
- transformující růstový faktor beta3 metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Understanding the molecular and cellular processes involved in skin wound healing may pave the way for the development of innovative approaches to transforming the identified natural effectors into therapeutic tools. Based on the extensive involvement of the ga(lactoside-binding)lectin family in (patho)physiological processes, it has been well established that galectins are involved in a wide range of cell-cell and cell-matrix interactions. AREAS COVERED: In the present paper, we provide an overview of the biological role of galectins in repair and regeneration, focusing on four main phases (hemostasis, inflammation, proliferation, and maturation/remodeling) of skin repair using basic wound models (open excision vs. sutured incision). EXPERT OPINION: The reported data make a strong case for directing further efforts to treat excisional and incisional wounds differently. Functions of galectins essentially result from their modular presentation. In fact, Gal-1 seems to play a role in the early phases of healing (anti-inflammatory) and wound contraction, Gal-3 accelerates re-epithelization and increases tensile strength (scar inductor). Galectins have also become subject of redesigning by engineering to optimize the activity. Clinically relevant, these new tools derived from the carbohydrate recognition domain platform may also prove helpful for other purposes, such as potent antibacterial agglutinins and opsonins.
- MeSH
- galektiny * MeSH
- hemostáza MeSH
- hojení ran * MeSH
- lidé MeSH
- proliferace buněk MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fibroblasts are actively involved in the formation of granulation tissue and/or tumor stroma. These cells possess the potential to differentiate into myofibroblasts acquiring a highly contractile phenotype characterized by the expression of α-smooth muscle actin (SMA). Considering TGF-β1 as the main inducer of myofibroblast differentiation and horse chestnut extract (HCE) as an effective modulator of the wound healing, we have new evidence to demonstrate canonical TGF-β1/SMAD and non-canonical/non-SMAD signaling in normal fibroblasts, isolated from healthy human skin (human dermal fibroblasts - HDFs), and their malignant counterparts (CAFs) isolated from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using western blot and immunofluorescence. Our study revealed that HCE stimulated the deposition of fibronectin by BCC fibroblasts (BCCFs), an effect not seen in other studied fibroblasts. Moreover, HCE in combination with TGF-β1 showed a synergic effect on the presence of polymerized SMA-stress fibers, particularly visible in CAFs. Interestingly, the TGF-β1 exposure led to activation of the canonical SMAD signaling in HDFs and BCCFs, whereas treatment of SCC fibroblasts (SCCFs) resulted in activation of the non-canonical AKT and/or ERK1/2 signaling. In conclusion, we observed specific differences in signaling between HDFs and CAFs that should be considered when developing new therapeutic approaches targeting wound/tumor microenvironments.
- MeSH
- Aesculus * MeSH
- bazocelulární karcinom * MeSH
- buněčná diferenciace MeSH
- fibroblasty asociované s nádorem * MeSH
- fibroblasty MeSH
- kultivované buňky MeSH
- lidé MeSH
- myofibroblasty MeSH
- nádorové mikroprostředí MeSH
- rostlinné extrakty farmakologie MeSH
- spinocelulární karcinom * farmakoterapie MeSH
- transformující růstový faktor beta1 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Recent evidence indicates that targeting IL-6 provides broad therapeutic approaches to several diseases. In patients with cancer, autoimmune diseases, severe respiratory infections [e.g. coronavirus disease 2019 (COVID-19)] and wound healing, IL-6 plays a critical role in modulating the systemic and local microenvironment. Elevated serum levels of IL-6 interfere with the systemic immune response and are associated with disease progression and prognosis. As already noted, monoclonal antibodies blocking either IL-6 or binding of IL-6 to receptors have been used/tested successfully in the treatment of rheumatoid arthritis, many cancer types, and COVID-19. Therefore, in the present review, we compare the impact of IL-6 and anti-IL-6 therapy to demonstrate common (pathological) features of the studied diseases such as formation of granulation tissue with the presence of myofibroblasts and deposition of new extracellular matrix. We also discuss abnormal activation of other wound-healing-related pathways that have been implicated in autoimmune disorders, cancer or COVID-19.
- MeSH
- autoimunita MeSH
- autoimunitní nemoci * farmakoterapie MeSH
- COVID-19 * MeSH
- hojení ran MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * farmakoterapie MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
