Knockdown of lysyl oxidase like 1 inhibits the proliferation and pro-fibrotic effects of Transforming growth factor-β1-induced hypertrophic scar fibroblasts

2021 ◽  
Author(s):  
Mengxia Ying ◽  
Yan Chen ◽  
Bo Yuan
Keyword(s):  
Cell Cycle ◽  
Western Blot ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Lysyl Oxidase ◽  
Healing Process ◽  
Cell Cycle Distribution ◽  
Wound Healing Process ◽  
Matrix Deposition ◽  
Tgf Β1

Background: The excessive healing response during wound repair can result in hypertrophic scars (HS). Lysyl oxidase like 1 (LOXL1) has been reported to be associated with fibrosis via targeting TGF-β1 signaling. This study aimed to investigate the effect of LOXL1 on HS formation. Methods: The expression of LOXL1 in HS tissues and TGF-β1-induced HSFs was detected via RT-qPCR and western blot. LOXL1 was silenced in HSFs using transfection with short hairpin RNA (shRNA), then wound healing process including cell proliferation, cell cycle distribution, migration and extracellular matrix deposition along with Smad expression were measured by CCK-8, EdU staining, flow cytometry, transwell, immunofluorescence and western blot assays. Results: LOXL1 was up-regulated in HS tissues and TGF-β1-induced HSFs. Knockdown of LOXL1 inhibited proliferation and migration, but promoted cell cycle G0/G1 phase arrest in TGF-β1-induced HSFs. The increased expression of cyclin D1, CDK4, MMP2, MMP9, COL1A1, COL1A2, fibronectin, COL3A1, α-SMA, but decreased expression of p27, and the phosphorylation of Smad2 and Smad3 caused by TGF-β1 were also blocked by LOXL1 silence. Conclusions: Silence of LOXL1 could effectively inhibit TGF-β1-induced proliferation, migration and ECM deposition in HSFs via inactivating Smad pathway. Targeting LOXL1 may have future therapeutic implications for HS treatment.

Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin

2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.

Growth Factors and Ocular Scarring

2009 ◽  
Vol 03 (02) ◽  
pp. 58 ◽  
Author(s):  
James S Ellis ◽  
Daniel J Paull ◽  
Sumit Dhingra ◽  
Ashkan Khalili ◽  
Maria Notara ◽  
...  
Keyword(s):  
Growth Factors ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Control Cell ◽  
Scar Tissue ◽  
Scar Formation ◽  
Wound Healing Process ◽  
Tissue Formation ◽  
Matrix Deposition ◽  
Scar Tissue Formation

Growth factors play a part in every stage of the wound healing process that leads to scar tissue formation. Ocular scarring can cause decreased vision or blindness by virtue of the opaque nature of the new matrix that is deposited as scar tissue (as in the lens or cornea). In addition, the contractile nature of the ocular scar tissue is the most common cause of failed retinal attachment. Scar formation after glaucoma surgery can lead to surgery failure. Growth factors, particularly the transforming growth factor (TGF-βs), play a major role in scar tissue formation in the eye and induce the synthesis of growth factors that control cell migration, proliferation, enzyme production and matrix deposition. Neurotrophins are also neuroprotective and can delay ganglion cell death, thus delaying scar formation in the retina if retinal attachment is restored promptly. Growth factors can be seen as a major target for preventing ocular scarring in the future.

scholarly journals Article Commentary: Cornea as a Model for Testing CTGF-Based Antiscarring Drugs

2016 ◽  
Vol 7 ◽  
pp. BTRI.S19954 ◽  
Author(s):  
Sriniwas Sriram ◽  
Jennifer A. Tran ◽  
James D. Zieske
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Wound Healing Process ◽  
Loss Of Function ◽  
Tgf Β1 ◽  
Downstream Mediator

Scarring remains a serious complication of the wound healing process that can lead to the formation of excessive fibrous connective tissue in an organ or tissue leading to pain and loss of function. This process is mainly regulated by Transforming growth factor β1 (TGF-β1), which binds to receptors and induces its downstream mediator, Connective tissue growth factor (CTGF). The number of drugs targeting CTGF for treating scars has been on the rise in the past few years. The purpose of this article is to suggest the possibility of using cornea as a model for testing anti-CTGF therapies for scarring.

scholarly journals Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hafiz Muhammad Umer Farooqi ◽  
Bohye Kang ◽  
Muhammad Asad Ullah Khalid ◽  
Abdul Rahim Chethikkattuveli Salih ◽  
Kinam Hyun ◽  
...  
Keyword(s):  
Cell Culture ◽  
Liver Fibrosis ◽  
Real Time ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Cell Monolayer ◽  
Embedded Sensors ◽  
Matrix Deposition ◽  
Tgf Β1

AbstractHepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

scholarly journals Butyrate Prevents TGF-β1-Induced Alveolar Myofibroblast Differentiation and Modulates Energy Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 258
Author(s):  
Hyo Yeong Lee ◽  
Somi Nam ◽  
Mi Jeong Kim ◽  
Su Jung Kim ◽  
Sung Hoon Back ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Mitochondrial Dynamics ◽  
Tca Cycle ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Pulmonary Fibroblasts ◽  
Matrix Deposition ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by excessive collagen matrix deposition and extracellular remodeling. Signaling pathways mediated by fibrotic cytokine transforming growth factor β1 (TGF-β1) make important contributions to pulmonary fibrosis, but it remains unclear how TGF-β1 alters metabolism and modulates the activation and differentiation of pulmonary fibroblasts. We found that TGF-β1 lowers NADH and NADH/NAD levels, possibly due to changes in the TCA cycle, resulting in reductions in the ATP level and oxidative phosphorylation in pulmonary fibroblasts. In addition, we showed that butyrate (C4), a short chain fatty acid (SCFA), exhibits potent antifibrotic activity by inhibiting expression of fibrosis markers. Butyrate treatment inhibited mitochondrial elongation in TGF-β1-treated lung fibroblasts and increased the mitochondrial membrane potential (MMP). Consistent with the mitochondrial observations, butyrate significantly increased ADP, ATP, NADH, and NADH/NAD levels in TGF-β1-treated pulmonary fibroblasts. Collectively, our findings indicate that TGF-β1 induces changes in mitochondrial dynamics and energy metabolism during myofibroblast differentiation, and that these changes can be modulated by butyrate, which enhances mitochondrial function.

Transforming growth factor-? isoforms differently stimulate pro?2 (I) collagen gene expression during wound healing process in transgenic mice

2002 ◽  
Vol 190 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Takuro Kinbara ◽  
Fumiaki Shirasaki ◽  
Shigeru Kawara ◽  
Yutaka Inagaki ◽  
Benoit de Crombrugghe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Wound Healing Process ◽  
Collagen Gene ◽  
Collagen Gene Expression

scholarly journals Role of Harmaline as Adiponectin Modulator in Defeating Liver Cirrhosis Induced By Thioacetamide in Mice

2021 ◽  
Vol 14 (1) ◽  
pp. 123-131
Author(s):  
Doha M. Beltagy ◽  
Khloud Gamal Abdelsalam ◽  
Tarek M Mohamed ◽  
Mai M. El-Keey
Keyword(s):  
Oxidative Stress ◽  
Liver Cirrhosis ◽  
Transforming Growth Factor Beta ◽  
Liver Tissue ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Matrix Deposition ◽  
Anti Inflammatory ◽  
Tgf Β1

Liver cirrhosis is currently the 11th most common cause of death which includes inflammatory, oxidative damage, and immune response. Harmaline has antioxidant and anti-inflammatory mechanisms which can defeat against hepatic cirrhosis pathways. The present work aimed to evaluate the ameliorating effect of harmaline against liver cirrhosis induced by thioacetamide in mice. The study was carried out on sixty male mice divided into three main groups. Control and harmaline groups (GIa and GIb), thioacetamide-group (GII) and harmaline co-treated and treated groups (GIIIa and GIIIb). By the end of the experiment, adiponectin concentrations were measured in serum and liver tissue. Gene expression of adiponectin, transforming growth factor beta-1 (TGF-β1), tissue inhibitor metalloprotease-1(TIMP-1) and peroxisome proliferator activated receptor-gamma (PPAR-γ) were assessed. Some oxidative stress biomarkers as malondialdehyde, reduced glutathione, catalase, superoxide dismutase and nitric oxide were determined. The results indicated that harmaline administration cause significant suppression of oxidative stress and inflammatory response.Inhibition of hepatic stellate cell activation and extracellular matrix deposition were also noticed with a significant decrease in the expression of the profibrotic markers(TGF-β1 and TIMP-1) which have direct effects on adiponectin activation. These results were confirmed by the histological studies in liver tissue. In Conclusion,Harmaline has excellent protective role against liver cirrhosis induced by thioacetamide in mice via its antioxidant and anti-inflammatory properties.It can be therapeutically used as a safe liver support by a dose of 10 mg/kg after furtherin vivo studies.

scholarly journals Topical Saudi Arabia Talh honey (Acacia nilotica) on surgical wound healing activity

2020 ◽  
Author(s):  
Ahmed G. Hegazi ◽  
Faiz M. Al Guthami ◽  
Mohamed H. Basiouny ◽  
Ahmed F.M. Al Gethami
Keyword(s):  
Wound Healing ◽  
Saudi Arabia ◽  
Wound Repair ◽  
Healing Process ◽  
Bacterial Count ◽  
Tissue Growth ◽  
Acacia Nilotica ◽  
Total Bacterial Count ◽  
Wound Healing Process ◽  
Ifn Γ

Honey has been documented as the oldest traditional medicine. It has been effective in suppressing inflammation, wound repair enhancer, and rapid autolytic debridement. The aim of this investigation was to evaluate the role of Saudi Arabia Talh honey (Acacia nilotica) dressing as a good alternative in care of diabetic foot (DFU) healing activity for twenty patients, wound total bacterial count, and serum cytokines levels (IFN-γ, IL-1, and IL-6). The results showed that Talh honey stimulates the wound healing process, broad-spectrum antibacterial activity, and reduction in the proinflammatory cytokines IFN-γ, IL-1, and IL-6 levels. It could be concluded that Talh honey bioactivities enhance wound healing by promoting tissue growth leading to wound repair, antibacterial, and reduction of inflammation.

scholarly journals The Role of Coconut Oil to Increase Expression of MMP-9, PDGF-BB, and TGF-β1 in NIH-3T3 Cell Line

2019 ◽  
Vol 7 (22) ◽  
pp. 3733-3736
Author(s):  
Dian Ika Perbina Meliala ◽  
Jansen Silalahi ◽  
Yuandani Yuandani ◽  
Linda Margata ◽  
Denny Satria
Keyword(s):  
Healing Process ◽  
Coconut Oil ◽  
Wound Healing Process ◽  
3T3 Cells ◽  
Virgin Coconut Oil ◽  
Nih3t3 Cells ◽  
Nih 3T3 ◽  
Tgf Β1 ◽  
Nih 3T3 Cells

AIM: The objective of the study was to evaluate protein expression in NIH 3T3 cells that are treated with virgin coconut oil (VCO) and hydrolysed of virgin coconut oil (HVCO) in vitro. METHODS: Coconut oil used in this study was virgin coconut oil (VCO) and VCO hydrolysed by Rhizomucor miehei (HVCO). NIH 3T3 cells (5x105 cells/well) were seeded in nine wells and incubated for overnight, then divided into three groups. Each group consisted of three wells. Group one without treatment, group two added VCO, and group three added HVCO and then incubated for overnight. One well in each group was added MMP-9, PDGF-BB, and TGF-β1 and incubated one hour. Finally, expressions of MMP-9, PDGF-BB, and TGF-β1 were detected using immunocytochemistry method. RESULTS: The results of the study showed that VCO and HVCO increased protein expressions of MMP-9, PDGF-BB, and TGF-β1. Percentage of MMP-9 expressions treated by VCO increased from 2.89 ± 0.07 to 28.16 ± 0.34, PDGF-BB from 28.11 ± 0.13 to 48.53 ± 0.49, and TGF-β1 from 4.19 ± 0.08 to 18.41 ± 0.54. Percentage of MMP-9 expressions treated by HVCO increased from 2.89 ± 0.07 to 55.40 ± 0.94, PDGF-BB from 28.11 ± 0.13 to 61.65 ± 0.42, and TGF-β1 from 4.19 ± 0.08 to 36.35 ± 0.67. CONCLUSION: VCO and HVCO increase the expression of MMP-9, PDGF-BB, dan TGF-β1 in NIH3T3 cells and therefore, coconut oil active in the wound healing process. HVCO is more than active than VCO.

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

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