TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts

Leduc, Chloé; Sobilo, Lauren; Toumi, Hechmi; Mondon, Philippe; Lespessailles, Éric; Ossant, Fédéric; Kurfürst, Robin; Pichon, Chantal

doi:10.1016/j.bbagen.2016.02.009

Cited by 11 publications

(8 citation statements)

References 47 publications

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“…; Andrianantoandro & Pollard, ; Leduc et al . ). In the absence of TGF‐β pre‐treatment, we found that BK triggered an approximately 50% de‐phosphorylation of cofilin, and that this effect was unaltered by the ARHGEF1 siRNA, suggesting no role for ARHGEF1, and therefore potentially no role for RhoA/Rho‐kinase, in the regulation of cofilin activity (Zhang et al .…”

Section: Discussionmentioning

confidence: 97%

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Transforming growth factor‐β enhances Rho‐kinase activity and contraction in airway smooth muscle via the nucleotide exchange factor ARHGEF1

Shaifta

Mackay

Irechukwu

et al. 2017

The Journal of Physiology

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Key points Transforming growth‐factor‐β (TGF‐β) and RhoA/Rho‐kinase are independently implicated in the airway hyper‐responsiveness associated with asthma, but how these proteins interact is not fully understood.We examined the effects of pre‐treatment with TGF‐β on expression and activity of RhoA, Rho‐kinase and ARHGEF1, an activator of RhoA, as well as on bradykinin‐induced contraction, in airway smooth muscle.TGF‐β enhanced bradykinin‐induced RhoA translocation, Rho‐kinase‐dependent phosphorylation and contraction, but partially suppressed bradykinin‐induced RhoA activity (RhoA‐GTP content).TGF‐β enhanced the expression of ARHGEF1, while a small interfering RNA against ARHGEF1 and a RhoGEF inhibitor prevented the effects of TGF‐β on RhoA and Rho‐kinase activity and contraction, respectively.ARHGEF1 expression was also enhanced in airway smooth muscle from asthmatic patients and ovalbumin‐sensitized mice.ARHGEF1 is a key TGF‐β target gene, an important regulator of Rho‐kinase activity and therefore a potential therapeutic target for the treatment of asthmatic airway hyper‐responsiveness. AbstractTransforming growth factor‐β (TGF‐β), RhoA/Rho‐kinase and Src‐family kinases (SrcFK) have independently been implicated in airway hyper‐responsiveness, but how they interact to regulate airway smooth muscle contractility is not fully understood. We found that TGF‐β pre‐treatment enhanced acute contractile responses to bradykinin (BK) in isolated rat bronchioles, and inhibitors of RhoGEFs (Y16) and Rho‐kinase (Y27632), but not the SrcFK inhibitor PP2, prevented this enhancement. In cultured human airway smooth muscle cells (hASMCs), TGF‐β pre‐treatment enhanced the protein expression of the Rho guanine nucleotide exchange factor ARHGEF1, MLC20, MYPT‐1 and the actin‐severing protein cofilin, but not of RhoA, ROCK2 or c‐Src. In hASMCs, acute treatment with BK triggered subcellular translocation of ARHGEF1 and RhoA and enhanced auto‐phosphorylation of SrcFK and phosphorylation of MYPT1 and MLC20, but induced de‐phosphorylation of cofilin. TGF‐β pre‐treatment amplified the effects of BK on RhoA translocation and MYPT1/MLC20 phosphorylation, but suppressed the effects of BK on RhoA‐GTP content, SrcFK auto‐phosphorylation and cofilin de‐phosphorylation. In hASMCs, an ARHGEF1 small interfering RNA suppressed the effects of BK and TGF‐β on RhoA‐GTP content, RhoA translocation and MYPT1 and MLC20 phosphorylation, but minimally influenced the effects of TGF‐β on cofilin expression and phosphorylation. ARHGEF1 expression was also enhanced in ASMCs of asthmatic patients and in lungs of ovalbumin‐sensitized mice. Our data indicate that TGF‐β enhances BK‐induced contraction, RhoA translocation and Rho‐kinase activity in airway smooth muscle largely via ARHGEF1, but independently of SrcFK and total RhoA‐GTP content. A role for smooth muscle ARHGEF1 in asthmatic airway hyper‐responsiveness is worthy of further investigation.

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Section: Discussionmentioning

confidence: 97%

“…; Leduc et al . ). Conversely, it has been suggested that, particularly in ASM, cofilin has an alternative role in promoting actin polymerization, perhaps independently of Rho‐kinase (Zhao et al .…”

Section: Introductionmentioning

confidence: 97%

Transforming growth factor‐β enhances Rho‐kinase activity and contraction in airway smooth muscle via the nucleotide exchange factor ARHGEF1

Shaifta

Mackay

Irechukwu

et al. 2017

The Journal of Physiology

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“…These responses are thought to be delayed under conditions of stress, such as prolonged metabolic stress or psychosocial stress [1], [3]. Although signaling pathways driven by cytokines such as the transforming growth factor beta (TGFβ) and interleukin 1 (IL1) are now known to play a role in cellular responses to injury, the molecular signals for cell-cell communication in the multicellular signaling network are still poorly understood [4], [5]. Besides cytokines, extracellular vesicles (EVs) were recently found to be released during the wounding of human epithelial cells in vitro [6].…”

Section: Introductionmentioning

confidence: 99%

Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress

et al. 2017

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BackgroundStress has demonstrated effects on inflammation though underlying cell-cell communication mechanisms remain unclear. We hypothesize that circulating RNAs and extracellular vesicles (EVs) in patients with chronic stress contain signals with functional roles in cell repair.MethodsBlood transcriptome from patients with Irritable Bowel Syndrome versus controls were compared to identify signaling pathways and effectors. Plasma EVs were isolated (size-exclusion chromatography) and characterized for effectors' presence (immunogold labelling-electron microscopy). Based on transcriptome pathways and EV-labelling, lysozyme's effects on cell migration were tested in human colon epithelial CRL-1790 cells and compared to the effects of CXCL12, a migration inducer (wound assay). The effect of lysozyme on immune-linked mRNA and protein levels in cells which survived following serum starvation and scratch wound were investigated (NanoString).ResultsBlood transcriptomes revealed pyridoxal 5’phosphate salvage, pyrimidine ribonucleotides salvage pathways, atherosclerosis, and cell movement signaling with membrane CD9 and extracellular lysozyme as effectors. Plasma EVs showed labelling with CD9, mucins, and lysozyme. This is the first identification of lysozyme on plasma EVs. In CRL-1790 cells, lysozyme induced migration and repaired scratch wound as well as CXCL12. Immune mRNA and protein expressions were altered in cells which survived following serum starvation and scratch wound, with or without lysozyme in serum-free media post-wounding: CD9, IL8, IL6 mRNAs and CD9, NT5E, PD-L1 proteins.ConclusionsRepair and inflammatory signals are identified in plasma EVs and circulating RNAs in chronic stress. Registered clinicaltrials.gov #NCT00824941General significanceThis study highlights the role of circulating RNAs and EVs in stress.

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“…Final differentiation of the hair follicles and hair structure are essential for wound repair . Among current treatments, Band‐aid adhesive bandages are used to prevent hemostasis, ointments containing antibiotics are used to prevented infections, and growth factors, eg bFGF, are used to promote fibroblasts proliferation . Recently, nanoparticles have been used as novel treatments in skin‐wound healing: silver nanoparticles are used as anti‐infection agents, while gold nanoparticles are used to stimulate fibroblast proliferation and collagen secretion .…”

Section: Discussionmentioning

confidence: 99%

Effect of the hyaluronic acid‐poloxamer hydrogel on skin‐wound healing: in vitro and in vivo studies

Li²,

Feng

et al. 2019

Anim Models and Exp Med

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Background Recent research into skin injury and wound healing has focused mainly on post‐trauma hemostasis, infection prevention, dermal regeneration and angiogenesis. However, less attention has been paid to air permeability and moisture loss prevention which also play important roles in injury healing. Methods In the present work, we prepared a hyaluronic acid‐poloxamer ( HA ‐ POL ) hydrogel and tested the therapeutic effect of the hydrogel on skin‐wound healing. Results The HA ‐ POL hydrogel transformed from sol to gel at 30°C, close to body temperature, and had stable moisturizing properties. HA ‐ POL hydrogel promoted skin‐wound healing and increased protein accumulation in the wound area. HA ‐ POL hydrogel allowed greater air permeability than Band‐aid, a typical wound covering. Results from transwell assays showed that the HA ‐ POL hydrogel effectively isolated skin‐wounds from bacterial invasion. Conclusion This work demonstrates the advantages of using HA ‐ POL gel materials in the treatment of cutaneous wounds.

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TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts

Cited by 11 publications

References 47 publications

Transforming growth factor‐β enhances Rho‐kinase activity and contraction in airway smooth muscle via the nucleotide exchange factor ARHGEF1

Transforming growth factor‐β enhances Rho‐kinase activity and contraction in airway smooth muscle via the nucleotide exchange factor ARHGEF1

Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress

Effect of the hyaluronic acid‐poloxamer hydrogel on skin‐wound healing: in vitro and in vivo studies

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