Tissue Barriers最新文献

Traumatic brain injury (TBI) is a leading cause of death and disability in patients. Brain microvasculature endothelial cells form the blood-brain barrier (BBB) which functions to maintain a protective barrier for the brain from the passive entry of systemic solutes. As a result of the cellular disruption caused by TBI, the BBB is compromised. Tight junction disruption in the endothelium of the BBB has been implicated in this response, but the underlying mechanisms remain unresolved. We utilized various in vivo models of severe to mild TBI as well as in vitro exposure of brain endothelial cells (bEND.3) to analyze conditions encountered following TBI to gain mechanistic insight into alterations observed at the BBB. We found that claudin-1 (CLDN1), was significantly increased in the brain endothelium both in vivo and in vitro. The observed increase of CLDN1 expression correlated with down-regulation of claudin-5 (CLDN5), occludin (OCLN), and zonula occludens (ZO-1), thereby altering BBB integrity by decreasing TEER and increasing permeability. Knockdown of CLDN1 in these pathogenic conditions showed stability of the endothelial junctional proteins. A decline in the epigenetic regulator silent information regulator family protein 1 (SIRT1), a member of the NAD+ dependent protein deacetylases, coincided with this upregulation of CLDN1. Indeed, the quenching of oxidative stress through NAC treatment was able to reduce injury-induced upregulation of CLDN1 in vitro. Mechanistically, an SRC-dependent tyrosine phosphorylation of OCLN and ZO-1 in CLDN1-modulated conditions was observed. Our findings will provide new insights into BBB deregulation and new possible treatment opportunities for TBI.

Several studies have focused on novel therapeutic strategies for extensive skin lesions aiming to improve healing quality and reduce treatment duration. In this context, the use of amniotic membrane (AM) and Wharton's jelly (WJ) emerges as promising alternatives. Full-thickness dorsal skin wounds were created in 21 Wistar rats, randomly divided into three groups: control (C), AM - covered by AM and WJ - covered by WJ. Wound contraction rate was measured weekly. On day 28, histochemical (Picrosirius red) and immunohistochemical analyses matrix metalloproteinase-9 (MMP-9), transforming growth factor beta (TGF-β), and alpha-smooth muscle actin (α-SMA) were performed. On day seven, wound contraction rate was higher in the AM group (38.8%), followed by the WJ (27.4%) and control (26.5%) with statistically significance. During the first 14 days, the AM group maintained the highest contraction rate, followed by the control and WJ groups. However, by day 21, wound contraction rates increased in the order of WJ to AM to control groups (85.6%, 87.0%, and 91.1%) with statistically significance. Type I collagen predominated across all groups, without statistically significant differences among them. TGF-β expression significantly increased from WJ to AM to control groups (19.75%, 26.00%, and 36.56%) with statistically significance. MMP-9 and α-SMA expressions decreased from control to WJ to AM groups, but no significant differences were observed. Both AM and WJ enhanced early wound contraction and may support skin repair by attenuating fibrotic signaling. These findings highlight the potential of AM and WJ as biomaterials for promoting tissue regeneration at epithelial barriers.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the result of an exaggerated inflammatory response triggered by a variety of pulmonary and systemic insults. The lung tissues are comprised of a variety of cell types, including alveolar epithelial cells, pulmonary vascular endothelial cells, macrophages, neutrophils, and others. There is mounting evidence that these diverse cell populations within the lung interact to regulate lung inflammation in response to both direct and indirect stimuli. The aim of this review is to provide a summary and discussion of recent advances in the understanding of the importance of cell-cell crosstalk in the pathogenesis of ALI/ARDS, with a specific focus on the cell-cell interactions that may offer prospective therapeutic avenues for ALI/ARDS.

Tight junctions (TJs) are an important component of cellular connectivity. Claudin family proteins, as a constituent of TJs, determine their barrier properties, cell polarity and paracellular permeability. Claudin-12 is an atypical member of the claudin family, as it belongs to the group of non-classical claudins that lack a PDZ-binding domain. It has been shown that claudin-12 is involved in paracellular Ca²⁺ transients and it is present in normal and hyperplastic tissues in addition to neoplastic tissues. Dysregulation of claudin-12 expression has been reported in various cancers, suggesting that this protein may play an important role in cancer cell migration, invasion, and metastasis. Some studies have shown that claudin-12 gene functions as a tumor suppressor, but others have reported that overexpression of claudin-12 significantly increases the metastatic properties of various tumor cells. Investigating this dual role of claudin-12 is of utmost importance and should therefore be studied in detail. The aim of this review is to provide an overview of the information available to date on claudin-12, including its structure, expression in various tissues and substances that may affect it, with a final focus on its role in cancer.

The development of efficient targeted therapies to ameliorate endothelial disorders is of the utmost need, as evident by the devastating outcomes of the recent pandemic. Recent findings suggest that unfolded protein response (UPR) modulates barrier function. In the current study, we reveal that the aforementioned highly conservative mechanism is involved in the protective effects of growth hormone-releasing hormone antagonists (GHRHAnt) in lung injury, both in vivo and in vitro. In bovine pulmonary artery endothelial cells, UPR suppression counteracted the protective effects of GHRHAnt in lipopolysaccharide (LPS)-induced endothelial hyperpermeability. In mouse lungs, UPR activation enhanced the beneficial effects of GHRHAnt against LPS-induced acute lung injury. Our observations - which are focused on lung endothelial cells and tissues - enhance our knowledge on the mechanisms mediating the barrier function and contribute to the development of novel therapies toward sepsis, direct and indirect lung injury. The effects of UPR modulation on the effects of GHRHAnt in other tissues are unknown, and they are the subject of future investigations.

Inflammatory bowel diseases (IBDs) are chronic conditions in which the digestive tract undergoes cycles of relapsing and remitting inflammatory episodes that cause patients to experience severe abdominal pain, bleeding, and diarrhea. Developing noninvasive and cost-effective surveillance methods that can detect an ensuing disease bout proffers an avenue to improve the quality of life for patients with IBD. Now, a recent report describes an ingenious, economical approach using a rationally designed Escherichia coli strain that can dynamically monitor inflammation inside the mammalian gastrointestinal tract. The ability of the engineered probiotic to specifically discern between dormant and activated inflammatory states of the digestive system demonstrates that living biosensors can be used to monitor health status, thus providing a powerful proof of concept that heralds the arrival of a new age of clinical diagnostics for people living with inflammatory diseases of the gut.

Crohn's disease (CD), a chronic gastrointestinal inflammatory disease, is becoming more widespread worldwide. Crohn's disease is caused by gut microbiota changes, genetics, environmental stresses, and immunological responses. Current treatments attempt to achieve long-term remission and avoid complications, delaying disease progression. Immunosuppressive measures and combination medicines should be started early for high-risk patients. These medicines monitor inflammatory indicators and adjust as needed. The epithelial barrier helps defend against physical, chemical, and immunological threats. When tissues' protective barrier breaks down, the microbiome may reach the layer underneath. Unbalanced microbial populations and inflammation impair healing and adjustment. Inflammatory cells infiltrating sensitive tissues aggravate the damage and inflammation. This approach promotes chronic inflammatory diseases. The epithelial barrier hypothesis states that hereditary and environmental variables cause epithelial tissue inflammation. This review focuses on how epithelial barrier break-down and microbial dysbiosis cause Crohn's disease and current advances in understanding the epithelial barrier, immune system, and microbiome. Additionally, investigate treatments that restore barrier integrity and promote microbial balance. Overall, it stresses the role of epithelial barrier failure and microbial dysbiosis in Crohn's disease development and discusses current advances in understanding the barrier, immunological responses, and microbiota.

Ulcerative colitis (UC) is a chronic and debilitating disorder that falls under the broad category of inflammatory bowel disease (IBD). Therefore, affects the colon and rectum, resulting in inflammation and ulcers in the lining of these organs. Over the years, there has been a significant shift in the management of UC. The focus has moved from achieving symptom-free daily living to attaining mucosal healing. Mucosal healing means completely restoring the colon and rectum's lining, significantly reducing the risk of complications and relapse. Macrophages are a crucial component of the immune system that play a vital role in the regeneration and repair of colonic ulcers. These immune cells are responsible for production of a variety of cytokines and growth factors that facilitate tissue repair. Macrophages are responsible for maintaining a balance between inflammation and healing. When this balance is disrupted, it can lead to chronic inflammation and tissue damage, exacerbating UC symptoms. Thus, this review aims to investigate the contribution of macrophages to mucosal repair and remission maintenance in UC patients.