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The liver is vulnerable to various hepatotoxins, including carbon tetrachloride (CCl4), which induces oxidative stress and apoptosis by producing reactive oxygen species (ROS) and activating the mitogen-activated protein kinase (MAPK) pathway. Cereblon (CRBN), a multifunctional protein implicated in various cellular processes, functions in the pathogenesis of various diseases; however, its function in liver injury remains unknown. We established a CRBN-knockout (KO) HepG2 cell line and examined its effect on CCl4-induced hepatocellular damage. CRBN-KO cells exhibited reduced sensitivity to CCl4-induced cytotoxicity, as evidenced by decreased levels of apoptosis markers, such as cleaved caspase-3, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. CRBN deficiency enhanced antioxidant defense, with increased superoxide dismutase activity and glutathione ratios (GSH/GSSG), as well as reduced pro-inflammatory cytokine expression. Mechanistically, the protective effects of CRBN deficiency appeared to involve the attenuation of the MAPK-mediated pathways, particularly through decreased phosphorylation of JNK and ERK. Overall, these results suggest the crucial role of CRBN in mediating the hepatocellular response to oxidative stress and inflammation triggered by CCl4 exposure, offering potential clinical implications for liver injury in a wide range of liver diseases.
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Proteínas Adaptadoras Transductoras de Señales , Apoptosis , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Estrés Oxidativo , Humanos , Apoptosis/efectos de los fármacos , Células Hep G2 , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Estrés Oxidativo/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/deficiencia , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αßγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.
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Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver disease, alcoholic hepatitis, chronic hepatitis, liver fibrosis, and cirrhosis, underscore the need for comprehensive research. Existing challenges in mimicking chronic alcohol exposure in cellular systems, attributed to ethanol evaporation, necessitate innovative approaches. In this study, we developed a simple, reusable, and controllable device for examining the physiological reactions of hepatocytes to long-term alcohol exposure. Our approach involved a novel device designed to continuously release ethanol into the culture medium, maintaining a consistent ethanol concentration over several days. We evaluated device performance by examining gene expression patterns and cytokine secretion alterations during long-term exposure to ethanol. These patterns were correlated with those observed in patients with alcoholic hepatitis. Our results suggest that our ethanol-releasing device can be used as a valuable tool to study the mechanisms of chronic alcohol-mediated hepatic diseases at the cellular level. Our device offers a practical solution for studying chronic alcohol exposure, providing a reliable platform for cellular research. This innovative tool holds promise for advancing our understanding of the molecular processes involved in chronic alcohol-mediated hepatic diseases. Future research avenues should explore broader applications and potential implications for predicting and treating alcohol-related illnesses.
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Periprosthetic joint infection (PJI) can be diagnosed to characterize the microorganisms constituting a biofilm, which is an essential procedure for proper treatment. The gold standard method for detecting and identifying the causative microorganism is culture of microorganisms from patients-derived sample.; however, this method takes a long time and has low sensitivity. To compensate for these limitations, identification methods based on real-time PCR (RT-PCR) have been widely used. However, RT-PCR also has limitations, including low sensitivity and the requirement of a standard curve for quantification. Therefore, to prevent significant proliferation of pathogenic bacteria, it is important to detect a limited number of infectious bacteria during early stages of PJI. In the present study, we developed droplet digital PCR-based detection of bacterial pathogens in PJI. And we evaluated the analytical performance of the assay using a model plasmid, based on the 16S ribosomal DNA sequence of target bacteria commonly found in PJI. We also prepared genomic DNA extracted from E. coli, S. aureus, and S. epidermidis to test whether ddPCR provides better sensitivity and quantification of the target sequences. ddPCR detected 400 attograms of target DNA, which was more than 10 times less than that detected by real-time PCR using synthesized plasmid. In addition, ddPCR detected target regions from genomic DNA of 50 femtograms for E. coli, 70 femtograms for S. epidermidis, and 90 femtograms for S. aureus. The results indicate that ddPCR has the potential to decrease the microbial detection limit and provide precise detection, signifying its effectiveness for early PJI.
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Artritis Infecciosa , Escherichia coli , Humanos , Escherichia coli/genética , Staphylococcus aureus/genética , Plásmidos/genética , Bacterias/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ADN RibosómicoRESUMEN
Breast cancer is a common tumor type among women, with a high fatality due to metastasis. Metastasis suppressors encode proteins that inhibit the metastatic cascade independent of the primary tumor growth. Raf kinase inhibitory protein (RKIP) is one of the promising metastasis suppressor candidates. RKIP is reduced or lost in aggressive variants of different types of cancer. A few pre-clinical or clinical studies have capitalized on this protein as a possible therapeutic target. In this article, we employed two breast cancer cells to highlight the role of RKIP as an antimetastatic gene. One is the low metastatic MCF-7 with high RKIP expression, and the other is MDA-MB-231 highly metastatic cell with low RKIP expression. We used high-throughput data to explore how RKIP is lost in human tissues and its effect on cell mobility. Based on our previous work recapitulating the links between RKIP and SNAI, we experimentally manipulated RKIP in the cell models through its novel upstream NME1 and investigated the subsequent genotypic and phenotypic changes. We also demonstrated that RKIP explained the uneven migration abilities of the two cell types. Furthermore, we identified the regulatory circuit that might carry the effect of an existing drug, Epirubicin, on activating gene transcription. In conclusion, we propose and test a potential strategy to reverse the metastatic capability of breast cancer cells by chemically manipulating RKIP expression.
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Interest in foods that promote inner beauty increases with increases in exposure to ultraviolet (UV) rays and with improvements in quality of life. This study was performed to evaluate the efficacy of fermented and aged mountain-cultivated ginseng sprouts (FAMCGSs), which have higher anti-inflammatory and antioxidant effects compared to mountain-cultivated ginseng sprouts (MCGSs), as an inner beauty enhancing food. The effect of orally administered FAMCGSs on UV type B (UVB) radiation-induced skin aging was investigated in a hairless mouse model through analyzing skin parameters including epidermal thickness, transepidermal water loss (TEWL), roughness, moisture, elasticity, and collagen contents. The mice exposed to UVB had markedly greater epidermal thickness, TEWL, and skin roughness than those of the normal control (NC) group. In addition, the levels of collagen, skin moisture, and dermal elasticity were lower in the UVB radiation group than the NC group. These UVB-induced skin aging parameters were significantly lower in the groups administered FAMCGSs than in the groups not administered FAMCGSs (p < 0.05). These results show that FAMCGSs exhibit a photoprotective effect in mice exposed to UVB and suggest that FAMCGSs can be used as a food that promotes inner beauty and protects skin from UVB-induced photoaging.
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Panax , Envejecimiento de la Piel , Animales , Ratones , Rayos Ultravioleta/efectos adversos , Ratones Pelados , Calidad de Vida , Piel , Colágeno/farmacología , Extractos Vegetales/farmacologíaRESUMEN
Autophagy is a degradative process to remove damaged or unnecessary cellular components, and it has been implicated in many biological processes during cell survival and death [...].
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Autofagia , Supervivencia CelularRESUMEN
Circadian rhythm regulates physiological cycles of awareness and sleepiness. Melatonin production is primarily regulated by circadian regulation of gene expression and is involved in sleep homeostasis. If the circadian rhythm is abnormal, sleep disorders, such as insomnia and several other diseases, can occur. The term 'autism spectrum disorder (ASD)' is used to characterize people who exhibit a certain set of repetitive behaviors, severely constrained interests, social deficits, and/or sensory behaviors that start very early in life. Because many patients with ASD suffer from sleep disorders, sleep disorders and melatonin dysregulation are attracting attention for their potential roles in ASD. ASD is caused by abnormalities during the neurodevelopmental processes owing to various genetic or environmental factors. Recently, the role of microRNAs (miRNAs) in circadian rhythm and ASD have gained attraction. We hypothesized that the relationship between circadian rhythm and ASD could be explained by miRNAs that can regulate or be regulated by either or both. In this study, we introduced a possible molecular link between circadian rhythm and ASD. We performed a thorough literature review to understand their complexity.
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Oxidative stress has been demonstrated to play a pivotal role in the pathological processes of many neurodegenerative diseases. In the present study, we demonstrated that Chrysanthemum boreale Makino extract (CBME) suppresses oxidative stress-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanism. Our observations revealed that CBME effectively protected neuronal cells against H2O2-induced cell death by preventing caspase-3 activation, Bax upregulation, Bcl-2 downregulation, activation of three mitogen-activated protein kinases (MAPKs), cAMP response element-binding protein (CREB) and NF-κB phosphorylation, and iNOS induction. These results provide evidence that CBME has remarkable neuroprotective properties in SH-SY5Y cells against oxidative damage, suggesting that the complementary or even alternative role of CBME in preventing and treating neurodegenerative diseases is worth further studies.
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Chrysanthemum , Neuroblastoma , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Apoptosis , Línea Celular Tumoral , Supervivencia Celular , Chrysanthemum/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Neuroblastoma/patología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
RATIONALE: Spontaneous retroperitoneal hematomas due to anticoagulant therapy rarely occur. Retroperitoneal hematomas can cause severe pain in the groin, quadriceps femoris muscle weakness, hemodynamic instability, and abdominal distension. They rarely cause compressive neuropathy of the femoral nerve transversing the iliacus muscle. Differential diagnosis is not easy because they have similar clinical features to retroperitoneal hematomas. PATIENT CONCERNS: A 72-year-old female patient whose right arm was stuck in a bookshelf for 5âdays developed right cephalic vein thrombosis. After 5âdays of intravenous heparin therapy for venous thrombosis, she presented with sudden right groin pain, right leg paresis, hemodynamic instability, and abdominal distension. DIAGNOSIS: Emergency abdominal and pelvic CT showed a large number of hematomas in the bilateral retroperitoneal space with active bleeding of the right lumbar artery. An electrodiagnostic study was performed 2âweeks later to check for neuromuscular damage in the right lower extremity, and right compressive femoral neuropathy was confirmed. INTERVENTIONS: Heparin therapy was discontinued; emergency embolization of the lumbar artery was performed. After 2âweeks, the patient started receiving physical, occupational, and transcutaneous electrical stimulation therapies. OUTCOMES: She became hemodynamically stable after arterial embolization; a significant decrease in hematoma and patency of the femoral nerve was confirmed on follow-up pelvic MRI. After 2âmonths of comprehensive rehabilitation, the muscle strength of the right leg significantly improved, and the pain disappeared. LESSONS: Although rare, spontaneous retroperitoneal hematomas may occur in patients receiving anticoagulant medications. They may even occur in patients receiving emergency anticoagulant therapy. Compressive femoral neuropathy due to retroperitoneal hematomas should be considered if muscle weakness and groin pain are observed. Early diagnosis and appropriate treatment plan of compressive femoral neuropathy due to retroperitoneal hematoma are helpful for a good prognosis.
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Neuropatía Femoral , Síndromes de Compresión Nerviosa , Anciano , Anticoagulantes/efectos adversos , Femenino , Neuropatía Femoral/etiología , Hematoma/inducido químicamente , Hematoma/complicaciones , Hematoma/terapia , Humanos , Síndromes de Compresión Nerviosa/etiología , MusloRESUMEN
BACKGOUND: Autophagy controls levels of cellular components during normal and stress conditions; thus, it is a pivotal process for the maintenance of cell homeostasis. In cancer, autophagy protects cells from cancerous transformations that can result from genomic instability induced by reactive oxygen species or other damaged components, but it can also promote cancer survival by providing essential nutrients during the metabolic stress condition of cancer progression. However, the molecular mechanism underlying autophagy-dependent regulation of the epithelial to mesenchymal transition (EMT) and metastasis is still elusive. METHODS: The intracellular level of NOTCH1 intracellular domain (NICD) in several cancer cells was studied under starvation, treatment with chloroquine or ATG7-knockdown. The autophagy activity in these cells was assessed by immunocytochemistry and molecular analyses. Cancer cell migration and invasion under modulation of autophagy were determined by in vitro scratch and Matrigel assays. RESULTS: In the study, autophagy activation stimulated degradation of NICD, a key transcriptional regulator of the EMT and cancer metastasis. We also found that NICD binds directly to LC3 and that the NICD/LC3 complex associates with SNAI1 and sequestosome 1 (SQSTM1)/p62 proteins. Furthermore, the ATG7 knockdown significantly inhibited degradation of NICD under starvation independent of SQSTM1-associated proteasomal degradation. In addition, NICD degradation by autophagy associated with the cellular level of SNAI1. Indeed, autophagy inhibited nuclear translocation of NICD protein and consequently decreased the transcriptional activity of its target genes. Autophagy activation substantially suppressed in vitro cancer cell migration and invasion. We also observed that NICD and SNAI1 levels in tissues from human cervical and lung cancer patients correlated inversely with expression of autophagy-related proteins. CONCLUSIONS: These findings suggest that the cellular level of NICD is regulated by autophagy during cancer progression and that targeting autophagy-dependent NICD/SNAI1 degradation could be a strategy for the development of cancer therapeutics.
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RATIONALE: Complex regional pain syndrome (CRPS) is a painful condition classified as type I or II depending on the absence or presence of nerve injury, respectively. Injury to the lateral dorsal cutaneous nerve (LDCN), a branch of the sural nerve, is a rare occurrence observed after a sprain or procedures conducted on the lateral side of the ankle. PATIENT CONCERNS: A 38-year-old female, who had undergone prolotherapy for a sprain in the lateral side of the left ankle 3âmonths ago, presented with persistent causalgia and dysesthesia around the injection site. DIAGNOSIS: An electrodiagnostic study was conducted, which confirmed that the patient had peripheral neuropathy of the left LDCN. Considering the digital infrared thermal imaging and three-phase bone scan findings and the clinical presentation, the condition was diagnosed as CRPS type II due to iatrogenic LDCN injury according to the Budapest diagnostic criteria for CRPS. INTERVENTIONS: The patient was treated with steroid pulse therapy, physical therapy, and transcutaneous electrical nerve stimulation, as well as nonsteroidal anti-inflammatory drugs, pregabalin, and tricyclic antidepressants. OUTCOMES: After 1âmonth of treatment, allodynia of the left foot persisted, but the pain reduced from 6 points to 3 points on the numeric rating scale. Partial recovery of amplitude and conduction velocity was confirmed in the follow-up electrodiagnostic study. LESSONS: LDCN injury should be considered in patients who complain of persistent lateral ankle and foot paresthesia or pain after sprain or procedures performed on the lateral side of the ankle. Early diagnosis and treatment can lead to a good prognosis when the LDCN injury has progressed to CRPS.
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Causalgia , Síndromes de Dolor Regional Complejo/diagnóstico , Parestesia , Traumatismos de los Nervios Periféricos , Proloterapia/efectos adversos , Adulto , Síndromes de Dolor Regional Complejo/etiología , Femenino , Humanos , Enfermedad Iatrogénica , Dolor , Esguinces y Distensiones/terapiaRESUMEN
Many diseases that involve malignant tumors in the elderly affect the quality of human life; therefore, the relationship between aging and pathogenesis in geriatric diseases must be under-stood to develop appropriate treatments for these diseases. Recent reports have shown that epigenetic regulation caused by changes in the local chromatin structure plays an essential role in aging. This review provides an overview of the roles of telomere shortening on genomic structural changes during an age-dependent shift in gene expression. Telomere shortening is one of the most prominent events that is involved in cellular aging and it affects global gene expression through genome rearrangement. This review provides novel insights into the roles of telomere shortening in disease-affected cells during pathogenesis and suggests novel therapeutic approaches.
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Envejecimiento , Epigénesis Genética , Regulación de la Expresión Génica , Neoplasias/patología , Telómero/química , Telómero/genética , Animales , Humanos , Neoplasias/genéticaRESUMEN
Drug screening strategies focus on quantifying the phenotypic effects of different compounds on biological systems. High-throughput technologies have the potential to understand further the mechanisms by which these drugs produce the desired outcome. Reverse causal reasoning integrates existing biological knowledge and measurements of gene and protein abundances to infer their function. This approach can be employed to appraise the existing biological knowledge and data to prioritize targets for cancer therapies. We applied text mining and a manual literature search to extract known interactions between several metastasis suppressors and their regulators. We then identified the relevant interactions in the breast cancer cell line MCF7 using a knockdown dataset. We finally adopted a reverse causal reasoning approach to evaluate and prioritize pathways that are most consistent and responsive to drugs that inhibit cell growth. We evaluated this model in terms of agreement with the observations under treatment of several drugs that produced growth inhibition of cancer cell lines. In particular, we suggested that the metastasis suppressor PEBP1/RKIP is on the receiving end of two significant regulatory mechanisms. One involves RELA (transcription factor p65) and SNAI1, which were previously reported to inhibit PEBP1. The other involves the estrogen receptor (ESR1), which induces PEBP1 through the kinase NME1. Our model was derived in the specific context of breast cancer, but the observed responses to drug treatments were consistent in other cell lines. We further validated some of the predicted regulatory links in the breast cancer cell line MCF7 experimentally and highlighted the points of uncertainty in our model. To summarize, our model was consistent with the observed changes in activity with drug perturbations. In particular, two pathways, including PEBP1, were highly responsive and would be likely targets for intervention.
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Chlorogenic acid is one of the most abundant polyphenols found in human diet. It is well-documented that chlorogenic acid has a significant impact on human cells, especially in the regulation of inflammation and metabolic processes. However, its role in regulating skin functions, especially with respect to the dermal collagen network or epidermal skin barrier, has not yet been elucidated. Here, we report that chlorogenic acid treatment can induce production of procollagen type I in human dermal fibroblast, Hs68 cell lines. Moreover, this treatment can stimulate upregulation of skin barrier genes, including the ones encoding filaggrin (FLG), involucrin (IVL), and envoplakin (EVPL), in epidermal keratinocytes. Chlorogenic acid also triggered a multifaceted response in the cytokine profile of keratinocytes. Therefore, we suggest that chlorogenic acid can be used to restore the impaired dermal matrix network as well as the epidermal skin barrier.
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Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood-brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient ß-catenin accumulation. Downregulated ß-catenin resulted in the reduction in stemness and cell growth in glioblastoma.
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Alcohol is one of the main causes of liver diseases such as fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis. To reproduce the conditions of alcohol-induced liver diseases and to identify the disease-causing mechanisms at the cellular level, several methods have been used to expose the cells to ethanol. As ethanol evaporates easily, it is difficult to mimic chronic alcohol exposure conditions at the cellular level. In this study, we developed a glass capillary system containing ethanol, which could steadily release ethanol from the polyethylene tubing and hydrogel portion at both sides of the capillary. The ethanol-containing capillary could release ethanol in the cell culture medium for up to 144 h, and the concentration of ethanol in the cell culture medium could be adjusted by controlling the number of capillaries. A long-term exposure to ethanol by the capillary system led to an increased toxicity of cells and altered the cellular physiologies, such as increasing the lipid accumulation and hepatic transaminase release in cells, as compared to the traditional direct ethanol addition method. Ethanol capillaries showed different gene expression patterns of lipid accumulation- or chronic alcoholism-related genes. Our results suggest that our ethanol-containing capillary system can be used as a valuable tool for studying the mechanism of chronic alcohol-mediated hepatic diseases at the cellular level.
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Hepatopatías Alcohólicas/patología , Modelos Biológicos , Etanol/toxicidad , Células Hep G2 , HumanosRESUMEN
Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of the disease-causing RNA or proteins encoded by these genes form aggregates and disrupt cellular function related to RNA metabolism. Disease-related RNA or proteins interact or sequester other RNA-binding proteins. Eventually, many disease-causing mutations lead to the dysregulation of nucleocytoplasmic shuttling, the dysfunction of stress granules, and the altered dynamic function of the nucleolus as well as other membrane-less organelles. As RNA-binding proteins are usually components of several RNA-binding protein complexes that have other roles, the dysregulation of RNA-binding proteins tends to cause diverse forms of cellular dysfunction. Therefore, understanding the role of RNA-binding proteins will help elucidate the complex pathophysiology of ALS. Here, we summarize the current knowledge regarding the function of disease-associated RNA-binding proteins and their role in the dysfunction of membrane-less organelles.
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Esclerosis Amiotrófica Lateral/metabolismo , Proteínas de Unión al ARN/metabolismo , Humanos , ARN/metabolismoRESUMEN
Physiological oxygen concentration (physioxia) ranges from 1 to 8% in human tissues while many researchers cultivate mammalian cells under an atmospheric concentration of 21% (hyperoxia). Oxygen is one of the significant gases which functions in human cells including energy production in mitochondria, metabolism in peroxidase, and transcription of various genes in company with HIF (Hypoxia-inducible factors) in the nucleus. Thus, mammalian cell culture should be deliberated on the oxygen concentration to mimic in vivo physiology. Here, we studied if the cultivation of human skin cells under physiological conditions could affect skin significant genes in barrier functions and dermal matrix formation. We further examined that some representative active ingredients in dermatology such as glycolic acid, gluconolactone, and salicylic acid work in different ways depending on the oxygen concentration. Taken together, we present the importance of oxygen concentration in skin cell culture for proper screening of novel ingredients as well as the mechanistic study of skin cell regulation.
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Hidroxiácidos/farmacología , Oxígeno/farmacología , Piel , Línea Celular , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Proteínas Filagrina , Regulación de la Expresión Génica , Gluconatos/metabolismo , Glicolatos/metabolismo , Humanos , Queratina-1/genética , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Lactonas/metabolismo , Metaloproteinasa 1 de la Matriz/genética , Oxígeno/metabolismo , ARN Mensajero/análisis , ARN Mensajero/genética , Proteínas S100/genética , Ácido Salicílico/metabolismo , Piel/citología , Piel/efectos de los fármacos , Piel/metabolismoRESUMEN
Inspired by the effectiveness of low-intensity ultrasound on tissue regeneration, we investigated the potential effect of short-term high-intensity ultrasound treatment for acceleration of wound healing in an in vitro wound model and dermal equivalent, both comprising human dermal fibroblasts. Short-term ultrasound of various amplitudes significantly increased the proliferation and migration of fibroblasts and subsequently increased the production of the extracellular matrix components fibronectin and collagen type I, both of which are important for wound healing and are secreted by fibroblasts. In addition, ultrasound treatment increased the contraction of a fibroblast-embedded three-dimensional collagen matrix, and the effect was synergistically increased in the presence of TGF-ß. RNA-sequencing and bioinformatics analyses revealed changes in gene expression and p38 and ERK1/2 MAPK pathway activation in the ultrasound-stimulated fibroblasts. Our findings suggest that ultrasound as a mechanical stimulus can activate human dermal fibroblasts. Therefore, the activation of fibroblasts using ultrasound may improve the healing of various types of wounds and increase skin regeneration.