Dataset Information

LC-MS/MS of baicalein-regulated human lung fibroblast

ABSTRACT: Here, we showed that baicalein suppressed transforming growth factor β1 (TGF β1)-stimulated the production of type I collagen in lung fibroblast MRC-5 cells. By applying SILAC-based proteomic technology, 158 proteins were identified as baicalein-modulated proteins in TGF β1-stimulated the accumulation of type I collagen in MRC-5 cells. Our proteomic and biochemical analysis demonstrated that baicalein could decrease the expression levels of connective tissue growth factor (CTGF) in TGF β1-stimulated MRC-5 cells. In addition, CTGF overexpression elevated the levels of type I collagen in baicalein-treated fibroblasts. Moreover, our results demonstrated that baicalein-downregulated CTGF expression might be related with the decrease of Smad2 phosphorylation, but not SP1.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fibroblast

DISEASE(S): Pulmonary Fibrosis

SUBMITTER: Xiaogang Jiang

LAB HEAD: Xiaogang Jiang

PROVIDER: PXD016167 | Pride | 2020-09-21

REPOSITORIES: Pride

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Publications

Baicalein alleviated TGF β1-induced type I collagen production in lung fibroblasts via downregulation of connective tissue growth factor.

Sun Xionghua X Cui Xinjian X Chen Xihua X Jiang Xiaogang X

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20200912

Although we have reported that baicalein ameliorated bleomycin-induced pulmonary fibrosis in rats and inhibited fibroblast-to-myofibroblast differentiation, the mechanisms of the capability of baicalein to suppress the production of type I collagen in fibroblasts remains unclear. Here, we showed that baicalein suppressed transforming growth factor β1 (TGF β1)-stimulated the production of type I collagen in lung fibroblast MRC-5 cells. By applying SILAC-based proteomic technology, 158 proteins we ...[more]

PMID: 32932046

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Project description:Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation The interplay between PLS (Plasmin) and TSP1 (Thrombospondin-1) in TGF-β1 (Transforming growth factor-β1)is shown using mathematical modelling and in vitro experimentents. This model is described in the article: Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-β1. Venkatraman L, Chia SM, Narmada BC, White JK, Bhowmick SS, Forbes Dewey C Jr, So PT, Tucker-Kellogg L, Yu H. Biophys J. 2012 Sep 5;103(5):1060-8. Abstract: Transforming growth factor-β1 (TGF-β1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-β1 from its latent form provides spatiotemporal control over TGF-β1 signaling, but the current understanding of TGF-β1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-β1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-β1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-β1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-β1 positive feedback loop and causes an unexpected net decrease in TGF-β1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-β1. The TGF-β1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-β1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-β1 activation: a TSP1-mediated mode of high activation and a PLS-mediated mode of low activation. This switch suggests an explanation for the unexpected effects of the plasminogen activation system on TGF-β1 in fibrotic diseases in vivo, as well as novel prognostic and therapeutic approaches for diseases with TGF-β dysregulation. This model is hosted on BioModels Database and identified by: MODEL1303130000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Vocal fold (VF) fibrosis, often caused by phonosurgery, radiation, or trauma, leads to irreversible voice dysfunction due to excessive ECM deposition and increased tissue stiffness. VF fibrosis, a significant cause of chronic dysphonia, lacks FDA-approved treatments, highlighting the critical need for novel antifibrotic therapeutic. TGF-β1 is a major driver in the pathological transformation of fibroblasts into contractile myofibroblasts in VF fibrosis via SMAD3, YAP1, and integrin signaling pathways. These pathways lead to increased ACTA2 expression, excessive collagen production, and progressive tissue stiffening. Leveraging the principle that local cells respond to tissue-specific signals, our ECM hydrogel derived from decellularized vocal fold lamina propria (VFLP-ECM) reduced ACTA2 expression in TGF-β1 stimulated vocal fold fibroblasts, showcasing antifibrotic potential. In this study, we evaluated the therapeutic potential of VFLP-ECM hydrogel in a rabbit VF injury model—treatment involved VFLP-ECM or bovine type I collagen injections into VFs 7 days after injury, with evaluations at 28 days post-injury. We compared two VFLP-ECM formulations: a manual process (VFLP (man)) and an accelerated automated method (VFLP (au)). VFLP (man) showed more modulated fibrosis-associated gene expressions when compared to VFLP (au) and collagen. Proteomic analysis revealed that VFLP (man) preserves a broader array of bioactive proteins, such as vitronectin, crucial in TGF-β1 signaling and ECM remodeling. The transcriptomic analysis uncovered a downregulation of key fibrotic markers and potential inhibition of regulators such as SMAD3, YAP1, and MRTFA, alongside the upregulation of SMAD7, an inhibitor of TGF-β signaling. Notably, treatment with VFLP (man) resulted in vocal folds with similar stiffness as uninjured controls, whereas tissues treated with collagen or VFLP (au) remained stiffer, indicating incomplete mechanical recovery. These data provide the first in vivo evidence that VFLP-ECM hydrogel—mainly when produced via manual decellularization—attenuates fibrosis by disrupting biochemical and biomechanical drivers of myofibroblast activation.

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	Baicalein01.raw	Raw
	Baicalein02.raw	Raw
	Baicalein03.raw	Raw
	Baicalein_identifiedpeptides.txt	Txt
	Baicalein_identifiedproteinGroups.txt	Txt