Biological activities of novel lipid mediator sphingosine 1-phosphate in rat hepatic stellate cells

2000 ◽  
Vol 279 (2) ◽  
pp. G304-G310 ◽  
Author(s):  
Hitoshi Ikeda ◽  
Yutaka Yatomi ◽  
Mikio Yanase ◽  
Hiroaki Satoh ◽  
Hisato Maekawa ◽  
...  

Sphingosine 1-phosphate (S-1-P), a lipid mediator shown to be a ligand for G protein-coupled receptors (AGRs), endothelial differentiation gene (EDG)1, EDG3, and AGR16/EDG5, is stored in platelets and released on their activation. Platelet consumption occurs in acute liver injury. Hepatic stellate cells (HSCs) play an important role in wound healing. Effects of S-1-P on HSCs were investigated. S-1-P enhanced proliferation of culture-activated HSCs. The mitogenic effect was pertussis toxin sensitive, mitogen-activated protein kinase dependent, and more prominent at lower cell density. S-1-P increased contraction of collagen lattices containing HSCs, irrespective of activation state, in a C3 exotoxin-sensitive manner. mRNAs of EDG1 and AGR16, but not of EDG3, were detected in HSCs. In HSC activation, EDG1 mRNA levels were downregulated, whereas AGR16 mRNA levels were unchanged. Considering that HSCs are capable of production of extracellular matrices and modulation of blood flow in sinusoids, our results suggest that S-1-P may play a role in wound healing process in the liver.

Livers ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 263-285
Author(s):  
Siti Aishah Sulaiman ◽  
Vicneswarry Dorairaj ◽  
Khairun Nur Abdul Ghafar ◽  
Nor Azian Abdul Murad

Hepatic fibrosis is a reversible wound healing process following liver injury. Although this process is necessary for maintaining liver integrity, severe excessive extracellular matrix accumulation (ECM) could lead to permanent scar formation and destroy the liver structure. The activation of hepatic stellate cells (HSCs) is a key event in hepatic fibrosis. Previous studies show that most antifibrotic therapies focus on the apoptosis of HSCs and the prevention of HSC activation. Noncoding RNAs (ncRNAs) play a substantial role in HSC activation and are likely to be biomarkers or therapeutic targets for the treatment of hepatic fibrosis. This review summarizes and discusses the previously reported ncRNAs, including the microRNAs, long noncoding RNAs, and circular RNAs, highlighting their regulatory roles and interactions in the signaling pathways that regulate HSC activation in hepatic fibrosis.


Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1795
Author(s):  
Judith Salas-Oropeza ◽  
Manuel Jimenez-Estrada ◽  
Armando Perez-Torres ◽  
Andres Eliu Castell-Rodriguez ◽  
Rodolfo Becerril-Millan ◽  
...  

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. It is an endemic tree known as “aceitillo”, and the antibacterial and antifungal activity of its essential oil has been verified; it also acts as an anti-inflammatory. All of these reported biological activities make the essential oil of B. morelensis a candidate to accelerate the wound-healing process. The objective was to determine the wound-healing properties of B. morelensis’ essential oil on a murine model. The essential oil was obtained by hydro-distillation, and the chemical analysis was performed by gas chromatography-mass spectrometry (GC-MS). In the murine model, wound-healing efficacy (WHE) and wound contraction (WC) were evaluated. Cytotoxic activity was evaluated in vitro using peritoneal macrophages from BALB/c mice. The results showed that 18 terpenoid-type compounds were identified in the essential oil. The essential oil had remarkable WHE regardless of the dose and accelerated WC and was not cytotoxic. In vitro tests with fibroblasts showed that cell viability was dose-dependent; by adding 1 mg/mL of essential oil (EO) to the culture medium, cell viability decreased below 80%, while, at doses of 0.1 and 0.01 mg/mL, it remained around 90%; thus, EO did not intervene in fibroblast proliferation, but it did influence fibroblast migration when wound-like was done in monolayer cultures. The results of this study demonstrated that the essential oil was a pro-wound-healing agent because it had good healing effectiveness with scars with good tensile strength and accelerated repair. The probable mechanism of action of the EO of B. morelensis, during the healing process, is the promotion of the migration of fibroblasts to the site of the wound, making them active in the production of collagen and promoting the remodeling of this collagen.


Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2286 ◽  
Author(s):  
Sibusiso Alven ◽  
Xhamla Nqoro ◽  
Blessing Atim Aderibigbe

Some of the currently used wound dressings have interesting features such as excellent porosity, good water-absorbing capacity, moderate water vapor transmission rate, high drug loading efficiency, and good capability to provide a moist environment, but they are limited in terms of antimicrobial properties. Their inability to protect the wound from microbial invasion results in wound exposure to microbial infections, resulting in a delayed wound healing process. Furthermore, some wound dressings are loaded with synthetic antibiotics that can cause adverse side effects on the patients. Natural-based compounds exhibit unique features such as good biocompatibility, reduced toxicity, etc. Curcumin, one such natural-based compound, has demonstrated several biological activities such as anticancer, antibacterial and antioxidant properties. Its good antibacterial and antioxidant activity make it beneficial for the treatment of wounds. Several researchers have developed different types of polymer-based wound dressings which were loaded with curcumin. These wound dressings displayed excellent features such as good biocompatibility, induction of skin regeneration, accelerated wound healing processes and excellent antioxidant and antibacterial activity. This review will be focused on the in vitro and in vivo therapeutic outcomes of wound dressings loaded with curcumin.


2020 ◽  
Vol 21 (9) ◽  
pp. 3267
Author(s):  
Anna Hübbers ◽  
Julia Hennings ◽  
Daniela Lambertz ◽  
Ute Haas ◽  
Christian Trautwein ◽  
...  

Liver fibrosis is a wound healing process in response to chronic liver injury, which is characterized by the accumulation of extracellular collagen produced by Hepatic Stellate Cells (HSCs). This process involves cell cycle re-entry and proliferation of normally quiescent HSCs controlled by cyclins and associated cyclin-dependent kinases (Cdks). Cdk2 mediates the entry and progression through S-phase in complex with E-and A-type cyclins. We have demonstrated that cyclin E1 is essential for liver fibrogenesis in mice, but it is not known if this is dependent on Cdk2 or related Cdks. Here, we aimed to evaluate the benefit of the pan-Cdk inhibitor CR8 for treatment of liver fibrosis in vitro. CR8-treatment reduced proliferation and survival in immortalized HSC lines and in addition attenuated pro-fibrotic properties in primary murine HSCs. Importantly, primary murine hepatocytes were much more tolerant against the cytotoxic and anti-proliferative effects of CR8. We identified CR8 dosages mediating anti-fibrotic effects in primary HSCs without affecting cell cycle activity and survival in primary hepatocytes. In conclusion, the pharmacological pan-Cdk inhibitor CR8 restricts the pro-fibrotic properties of HSCs, while preserving proliferation and viability of hepatocytes at least in vitro. Therefore, CR8 and related drugs might be beneficial for the treatment of liver fibrosis.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Sabrina Valente ◽  
Carmen Ciavarella ◽  
Emanuela Pasanisi ◽  
Francesca Ricci ◽  
Andrea Stella ◽  
...  

Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers.


2019 ◽  
Vol 26 (31) ◽  
pp. 5825-5848 ◽  
Author(s):  
Nicoletta Polera ◽  
Mariateresa Badolato ◽  
Filomena Perri ◽  
Gabriele Carullo ◽  
Francesca Aiello

Giving a glance to the report of Wound Care Market by Product updated in 2017, we can see that wound care market is expected to reach USD 22.01 billion by 2022 from USD 18.35 billion at a CAGR of 3.7%. Numerous factors are driving the growth of this market, including the increasing prevalence of chronic wounds and acute wounds, increasing aged population, rising R&D activities and advancement in the field of wound care research. Advanced wound management products are accounted for the largest market share in 2017. These evidences mean that the wound care research represents a Clinical Emergency other than an interesting Marketing tool. Drug therapies so far fight efficaciously with the opportunistic pathologies derived from chronic wounds, although an unsolved challenge is still finding a useful remedy to correct the impaired wound healing process and overcome the chronic wound state, to avoid bacterial rising and severe pain. Traditional medicinal plants have been widely used in the management of wounds and different plant extracts have been evaluated for their wound healing properties through both in vitro and in vivo studies. Their phytochemical components in particular quercetin, contribute to their remedial properties in wound repair. Quercetin has important biological activities related to the improvement of the wound healing process. The present review discusses and focuses on the latest findings of the wound healing properties of quercetin, alone or as a part of plant extract, and its role as a new frontier in wound repair.


Author(s):  
Yidan Su ◽  
Min Li ◽  
Xiqiao Wang ◽  
Zhiyong Wang ◽  
Lei Yi

When exposed to thermal factors, collagen in the dermis denatures, which could affect the biological behavior of cells. Previous studies have demonstrated that denatured collagen could influence the activity of fibroblasts and induce fibroblasts differentiate into myofibroblasts. However, information on the regulation of fibroblasts by denatured collagen-modulated autophagy and apoptosis during the wound healing process is limited. In this article, we researched the effect of denatured collagen-modulated autophagy and apoptosis on fibroblasts. An in vitro model comprising fibroblasts and denatured collagen was established to identify the potential ability of denatured collagen to modulate autophagy and apoptosis. Western blotting, quantitative polymerase chain reaction, transmission electron microscopy, TUNEL assay, and immunofluorescence staining were used to examine the changes induced by denatured collage. Protein and mRNA levels of LC3 and beclin-1 were significantly increased after stimulated by denatured collagen, while those of caspase-3 were reduced. Unlike stimulation with normal collagen, denatured collagen enhanced autophagy and inhibited apoptosis of fibroblasts. After blocking autophagy using 3-methyladenine, the apoptotic function was increased. Denatured collagen could increase autophagy and inhibit apoptosis of the fibroblasts to promote cell survival and influence wound healing.


2021 ◽  
Author(s):  
Fei Yan ◽  
Meihua Gong ◽  
Furong Li ◽  
Li Yu

Abstract Background: Pressure ulcers (PU) are a chronic wound for elderly populations. Previous works have shown that exosomes from stem cells contain cytokines and growth factors that play a role in tissue repair and can represent a therapeutic strategy for wound healing. Thus, as a new cell-free treatment model, fully understanding the extraction of exosomes and its mechanism of action can help promote the management of clinically chronic refractory wound healing. Material and Methods: In this study, we initially isolated exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Exo) and examined their roles in wound healing. Different time points were evaluated for 15 mice which were randomly divided into three groups to serve three I-R circles and took different dose of hucMSC-Exo. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analyze collagen mRNA levels in tissue samples. HMGB1 content was explored by western blot and immunohistochemistry. Comparing α-SAM, CD34, HMGB1 were used to investigate the potential mechanisms.Results: We found that hucMSC-Exo could be taken up by fibroblasts and significantly regulate and improve fibroblast fibrotic status and in-vivo PU wound healing. Further, we observed that hucMSC-Exo treatment of PU wound was able to downregulate the expression of HMGB1 previously shown to have a deleterious role in the wound healing process. Conclusion: Our study indicates that hucMSC-Exo regulates the repair of pressure ulcer wounds in part by inhibiting HMGB1. Exosome treatment has opened up a new perspective in regenerative medicine and trauma management.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shuo Qiu ◽  
Yachao Jia ◽  
Yunchu Sun ◽  
Pei Han ◽  
Jia Xu ◽  
...  

Aims. The purpose of the present research is to investigate the effects of the VHL protein antagonist, VH298, on functional activities of fibroblasts and vascular endothelial cells and the effects on the wound healing process in a streptozotocin-induced hyperglycaemic rat model. Methods. HIF-1α and hydroxy-HIF-1α protein levels in VH298-treated rat fibroblasts (rFb) were measured by immunoblotting, rFb proliferation was detected by the CCK-8 assay, and mRNA levels of related genes were measured by quantitative RT-PCR. In vitro wound healing was simulated by the scratch test; angiogenesis was measured by the human umbilical vein endothelial cell (hUVEC) tube formation assay. VH298 or PBS was locally injected into wounds in rat models with streptozotocin- (STZ-) induced hyperglycaemia, the wound tissues were harvested, and haematoxylin-eosin (HE) and Masson trichrome staining and immunohistochemical processes were conducted. Results. HIF-1α and hydroxy-HIF-1α levels increased in VH298-treated rFb, in a time- and dose-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, angiogenesis, and gene expression of type I collagen-α1 (Col1-α1), vascular endothelial growth factor A (VEGF-A), and insulin-like growth factor 1 (IGF-1). The VH298-treated wound had a better healing pattern, activation of HIF-1 signalling, and vascularization. Conclusions. Taken together, VH298 activated the HIF-1 signalling pathway by stabilizing both HIF-1α and hydroxy-HIF-1α. VH298 enhanced rFb functions, promoted hUVEC angiogenesis, and accelerated wound healing in the rat model mimicking diabetes mellitus.


2019 ◽  
Vol 2 (1) ◽  
pp. 14-17
Author(s):  
Nurul Aini Siagian ◽  
Syafira Nusaibah ◽  
Andayani Boang Manalu

Early mobilization includes factors that can affect the process of wound healing after surgery. Immediate mobilization in stages is very useful for the process of healing wounds and preventing infection and venous thrombosis. The purpose of this study was to determine whether there is a relationship between early mobilization and the process of healing wound post operative sectio caesarea at Sinar Husni General Hospital Medan Helvetia. The research design used was analytic survey with cross sectional approach. The sample in this study used the Consecutive Sampling method of data collection using a checklist sheet conducted on a sample of 19 respondents. The results of the study in this study are the majority of respondents who did early mobilization and who experienced rapid wound healing process as many as 4 people (21%) while the minority of respondents who did early mobilization and who experienced slow wound healing process were 1 person (5.3%). The majority of respondents who did not mobilize early and who experienced a slow wound healing process were 11 people (57.9%) and a minority who did not mobilize early and who experienced rapid healing as many as 4 people (21.1%). Statistical test results obtained p value = 0.046 <0.005. The conclusions of the results of this study indicate there is a relationship between early mobilization and the process of healing post operative sectio of caesarea. Suggestions The results of this study can be applied as a reference to improve nursing care services, especially in providing counseling and assistance to patients.


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