RESUMEN
Treatment of chronic diabetic wounds is an ongoing socio-economic challenge. Dysregulated signalling pathways characterise cells from chronic diabetic wounds. Photobiomodulation (PBM) stimulates healing by eliciting photochemical effects that affect gene regulation. JAK/STAT signalling is a primary signal transduction pathway involved in wound healing. This in vitro study aimed to determine if PBM at 830 nm and a fluence of 5 J/cm2 regulates genes related to JAK/STAT signalling in wounded and diabetic wounded fibroblast cells. A continuous wave diode laser (12.53 mW/cm2 ) was used to irradiate cells. Forty-eight hours post-PBM, RT-qPCR was used to analyse 84 genes related to JAK/STAT signalling. Five genes were upregulated and four downregulated in wounded cell models, while six genes were downregulated in diabetic wounded models. The results show drastic gene expression differences between wounded and diabetic wounded cell models in response to PBM using 830 nm.
Asunto(s)
Diabetes Mellitus , Terapia por Luz de Baja Intensidad , Humanos , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Transducción de Señal , Fibroblastos/metabolismo , Expresión GénicaRESUMEN
Ageing and chronic degenerative pathologies demonstrate the shared characteristics of high bioavailability of reactive oxygen species (ROS) and oxidative stress, chronic/persistent inflammation, glycation, and mitochondrial abnormalities. Excessive ROS production results in nucleic acid and protein destruction, thereby altering the cellular structure and functional outcome. To stabilise increased ROS production and modulate oxidative stress, the human body produces antioxidants, "free radical scavengers", that inhibit or delay cell damage. Reinforcing the antioxidant defence system and/or counteracting the deleterious repercussions of immoderate reactive oxygen and nitrogen species (RONS) is critical and may curb the progression of ageing and chronic degenerative syndromes. Various therapeutic methods for ROS and oxidative stress reduction have been developed. However, scientific investigations are required to assess their efficacy. In this review, we summarise the interconnected mechanism of oxidative stress and chronic inflammation that contributes to ageing and chronic degenerative pathologies, including neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), cardiovascular diseases CVD, diabetes mellitus (DM), and chronic kidney disease (CKD). We also highlight potential counteractive measures to combat ageing and chronic degenerative diseases.
Asunto(s)
Enfermedades Cardiovasculares , Estrés Oxidativo , Envejecimiento , Antioxidantes/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Inflamación/tratamiento farmacológico , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Photobiomodulation (PBM) imparts therapeutically significant benefits in the healing of chronic wounds. Chronic wounds develop when the stages of wound healing fail to progress in a timely and orderly frame, and without an established functional and structural outcome. Therapeutic benefits associated with PBM include augmenting tissue regeneration and repair, mitigating inflammation, relieving pain, and reducing oxidative stress. PBM stimulates the mitochondria, resulting in an increase in adenosine triphosphate (ATP) production and the downstream release of growth factors. The binding of growth factors to cell surface receptors induces signalling pathways that transmit signals to the nucleus for the transcription of genes for increased cellular proliferation, viability, and migration in numerous cell types, including stem cells and fibroblasts. Over the past few years, significant advances have been made in understanding how PBM regulates numerous signalling pathways implicated in chronic wound repair. This review highlights the significant role of PBM in the activation of several cell signalling pathways involved in wound healing.
Asunto(s)
Terapia por Luz de Baja Intensidad/métodos , Cicatrización de Heridas , Animales , Proliferación Celular , Humanos , Transducción de SeñalRESUMEN
A disrupted wound repair process often leads to the development of chronic wounds, and pose a major physical, social and economic inconvenience on patients and the public health sector. Chronic wounds are a common complication seen in diabetes mellitus (DM), and often the severity necessitates amputation of the lower limbs. Recently, there has been increasing evidence that photobiomodulation (PBM) initiates wound healing, including increased protein transcription for cell proliferation, viability, migration and tissue reepithelialisation. Here, the hypothesis that PBM at a wavelength of 660 nm and energy density of 5 J/cm2 regulates wound repair in diabetic wounded and hypoxic diabetic wounded fibroblasts by enhancing cell migration and survival was investigated. PBM increased migration and survival in diabetic wounded and hypoxic diabetic wounded fibroblasts. Our findings suggest that PBM enhances migration and survival in diabetic wounded and hypoxic diabetic wounded fibroblasts, indicating that this therapeutic method may be beneficial against chronic wounds in diabetic patients.
Asunto(s)
Movimiento Celular/efectos de la radiación , Diabetes Mellitus/patología , Fibroblastos/patología , Fibroblastos/efectos de la radiación , Hipoxia/patología , Terapia por Luz de Baja Intensidad , Animales , Apoptosis/efectos de la radiación , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Humanos , Cicatrización de Heridas/efectos de la radiaciónRESUMEN
Activated phosphatidylinositol 3 kinase/Protein kinase B (PI3K/AKT) signalling with increased or reduced mTOR and GSK3ß activity influences the wound repair process. Diabetic wounds, usually ulcerated, are characterised by reduced growth factors and cellular performance. The occurrence of diabetic ulcers is linked to peripheral arterial disease, neuropathy, and wound contamination. Lasers or light emitting diodes (LEDs) provide photon energy with therapeutic benefits (Photobiomodulation-PBM), and has been broadly commended to quicken diabetic wound healing. PBM is efficient in the visible red and near-infrared electromagnetic spectrum, and fluencies ranging from 2 to 6 J/cm2. However, cellular and molecular mechanisms induced by PBM are not fully understood. In this review we discuss PBM and the PI3K/AKT pathway with specific focus on the mTOR and GSK3ß downstream activity in diabetic wound healing.
Asunto(s)
Complicaciones de la Diabetes/radioterapia , Terapia por Luz de Baja Intensidad , Transducción de Señal , Cicatrización de Heridas , Heridas y Lesiones/radioterapia , Animales , Fibroblastos/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/inmunología , Humanos , Ratones , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Wound healing is a physiological process that occurs in overlapping phases namely hemostasis, inflammation, proliferation, and remodeling. Chronic wounds fail to proceed through these reparative processes to achieve the functional integrity within the expected time. Wound healing relies upon growth factors and cytokines for the precise and accurate regulation of cellular responses. These are achieved through the use of complex growth factor/cytokine induced signaling pathways. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway transmits extracellular signals to the nucleus for the transcription of genes involved in proliferation and differentiation, to name but a few. Photobiomodulation (PBM) is an emerging area of interest within the scientific community and researchers are currently exploring its underlying mechanism and the associated signaling pathways involved. PBM is a light based therapy making use of low powered lasers or light emitting diodes (LEDs) to enhance tissue repair, and reduce pain and inflammation. Current conventional treatments for chronic wounds are frequently associated with failure and have limited therapeutic efficacy. Thus there is a need for efficient wound healing interventions and the identification and development of new treatments is required. In this review we summarize the involvement of JAK/STAT signaling and PBM in chronic wounds.