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dc.contributor.authorXu, Hong
dc.contributor.authorYang, Fang
dc.contributor.authorSun, Ying
dc.contributor.authorYuan, Yuan
dc.contributor.authorCheng, Hua
dc.contributor.authorWei, Zhongqiu
dc.contributor.authorLi, Shuyu
dc.contributor.authorCheng, Tan
dc.contributor.authorBrann, Darrell W
dc.contributor.authorWang, Ruimin
dc.date.accessioned2012-10-26T20:30:47Z
dc.date.available2012-10-26T20:30:47Z
dc.date.issued2012-07-3en_US
dc.identifier.citationPLoS One. 2012 Jul 3; 7(7):e40301en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22802960en_US
dc.identifier.doi10.1371/journal.pone.0040301en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/804
dc.description.abstractBackground: Myofibroblast differentiation, characterized by a-smooth muscle actin (a-SMA) expression, is a key process in organ fibrosis, and is induced by TGF-b. Here we examined whether an anti-fibrotic agent, N-acetyl-seryl-aspartyllysylproline (Ac-SDKP), can regulate induction of TGF-b signaling and myofibroblast differentiation as a potential key component of its anti-fibrotic mechanism in vivo and in vitro.
dc.description.abstractMethodology/Principal Findings: Rat pulmonary fibroblasts were cultured in vitro and divided to 4 groups 1) control; 2) TGF-b1; 3) TGF-b1+ LY364947; 4) TGF-b1+Ac-SDKP. For in vivo studies, six groups of animals were utilized 1) control 4w; 2) silicotic 4w; 3) control 8w; 4) silicotic 8w; 5) Ac-SDKP post-treatment; 6)Ac-SDKP pre-treatment. SiO2 powders were douched in the trachea of rat to make the silicotic model. Myofibroblast differentiation was measured by examining expression of a- SMA, as well as expression of serum response factor (SRF), a key regulator of myofibroblast differentiation. The expressions of collagen, TGF-b1 and RAS signaling were also assessed. The results revealed that TGF-b1 strongly induced myofibroblast differentiation and collagen synthesis in vitro, and that pre-treatment with Ac-SDKP markedly attenuated myofibroblast activation, as well as induction of TGF-b1 and its receptor. Similar results were observed in vivo in the pathologically relevant rat model of silicosis. Ac-SDKP treatment in vivo strongly attenuated 1) silicosis-induced increased expressions of TGF-b1 and RAS signaling, 2) myofibroblast differentiation as indicated by a robust decrease of SRF and a-SMA-positive myofibroblast localization in siliconic nodules in the lung, 3) collagen deposition.
dc.description.abstractConclusion/Significance: The results of the present study suggest a novel mechanism of action for Ac-SDKP’s beneficial effect in silicosis, which involves attenuation of TGF-b1 and its receptors, SRF and Ang II type 1 receptor (AT1) expression, collagen deposition and myofibroblast differentiation. The results further suggest that therapies targeting myofibroblast differentiation may have therapeutic efficacy in treatment of silicosis of the lung.
dc.rightsXu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectImmune Physiologyen_US
dc.subjectCytokinesen_US
dc.subjectImmunologyen_US
dc.subjectImmune Systemen_US
dc.subjectCytokinesen_US
dc.subjectImmunityen_US
dc.subjectInflammationen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectSignal Transductionen_US
dc.subjectSignaling Cascadesen_US
dc.subjectTGF-beta signaling cascadeen_US
dc.subjectMedicineen_US
dc.subjectClinical Immunologyen_US
dc.subjectImmunityen_US
dc.subjectInflammationen_US
dc.subjectPulmonologyen_US
dc.subjectEnvironmental and Occupational Lung Diseasesen_US
dc.subjectPneumoconiosesen_US
dc.titleA New Antifibrotic Target of Ac-SDKP: Inhibition of Myofibroblast Differentiation in Rat Lung with Silicosisen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3389005en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics
refterms.dateFOA2019-04-10T00:55:52Z
html.description.abstractBackground: Myofibroblast differentiation, characterized by a-smooth muscle actin (a-SMA) expression, is a key process in organ fibrosis, and is induced by TGF-b. Here we examined whether an anti-fibrotic agent, N-acetyl-seryl-aspartyllysylproline (Ac-SDKP), can regulate induction of TGF-b signaling and myofibroblast differentiation as a potential key component of its anti-fibrotic mechanism in vivo and in vitro.
html.description.abstractMethodology/Principal Findings: Rat pulmonary fibroblasts were cultured in vitro and divided to 4 groups 1) control; 2) TGF-b1; 3) TGF-b1+ LY364947; 4) TGF-b1+Ac-SDKP. For in vivo studies, six groups of animals were utilized 1) control 4w; 2) silicotic 4w; 3) control 8w; 4) silicotic 8w; 5) Ac-SDKP post-treatment; 6)Ac-SDKP pre-treatment. SiO2 powders were douched in the trachea of rat to make the silicotic model. Myofibroblast differentiation was measured by examining expression of a- SMA, as well as expression of serum response factor (SRF), a key regulator of myofibroblast differentiation. The expressions of collagen, TGF-b1 and RAS signaling were also assessed. The results revealed that TGF-b1 strongly induced myofibroblast differentiation and collagen synthesis in vitro, and that pre-treatment with Ac-SDKP markedly attenuated myofibroblast activation, as well as induction of TGF-b1 and its receptor. Similar results were observed in vivo in the pathologically relevant rat model of silicosis. Ac-SDKP treatment in vivo strongly attenuated 1) silicosis-induced increased expressions of TGF-b1 and RAS signaling, 2) myofibroblast differentiation as indicated by a robust decrease of SRF and a-SMA-positive myofibroblast localization in siliconic nodules in the lung, 3) collagen deposition.
html.description.abstractConclusion/Significance: The results of the present study suggest a novel mechanism of action for Ac-SDKP’s beneficial effect in silicosis, which involves attenuation of TGF-b1 and its receptors, SRF and Ang II type 1 receptor (AT1) expression, collagen deposition and myofibroblast differentiation. The results further suggest that therapies targeting myofibroblast differentiation may have therapeutic efficacy in treatment of silicosis of the lung.


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