scholarly journals Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus

2022 ◽  
Vol 12 ◽  
Author(s):  
Jiachang Xu ◽  
Xue Yu ◽  
Hangyu Ye ◽  
Songze Gao ◽  
Niuniu Deng ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Vibrio Parahaemolyticus ◽  
Transforming Growth Factor ◽  
Takifugu Obscurus ◽  
Changing Trends ◽  
Model Animal ◽  
Comparative Metabolomics ◽  
Tgf Β1

Coronavirus disease 2019 (COVID-19) raises the issue of how hypoxia destroys normal physiological function and host immunity against pathogens. However, there are few or no comprehensive omics studies on this effect. From an evolutionary perspective, animals living in complex and changeable marine environments might develop signaling pathways to address bacterial threats under hypoxia. In this study, the ancient genomic model animal Takifugu obscurus and widespread Vibrio parahaemolyticus were utilized to study the effect. T. obscurus was challenged by V. parahaemolyticus or (and) exposed to hypoxia. The effects of hypoxia and infection were identified, and a theoretical model of the host critical signaling pathway in response to hypoxia and infection was defined by methods of comparative metabolomics and proteomics on the entire liver. The changing trends of some differential metabolites and proteins under hypoxia, infection or double stressors were consistent. The model includes transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and epidermal growth factor (EGF) signaling pathways, and the consistent changing trends indicated that the host liver tended toward cell proliferation. Hypoxia and infection caused tissue damage and fibrosis in the portal area of the liver, which may be related to TGF-β1 signal transduction. We propose that LRG (leucine-rich alpha-2-glycoprotein) is widely involved in the transition of the TGF-β1/Smad signaling pathway in response to hypoxia and pathogenic infection in vertebrates as a conserved molecule.

scholarly journals High-Throughput Screening Assay Identifies Small Molecules Capable of Modulating the BMP-2 and TGF-β1 Signaling Pathway

2016 ◽  
Vol 22 (1) ◽  
pp. 40-50 ◽  
Author(s):  
Corina-Adriana Ghebes ◽  
Jéré van Lente ◽  
Janine Nicole Post ◽  
Daniel B. F. Saris ◽  
Hugo Fernandes
Keyword(s):  
Growth Factor ◽  
Small Molecules ◽  
Signaling Pathways ◽  
High Throughput Screening ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Bone Morphogenetic Protein 2 ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Tgf Β1

Modulating the bone morphogenetic protein 2 (BMP-2) and transforming growth factor–β1 (TGF-β1) signaling pathways is essential during tendon/ligament (T/L) healing. Unfortunately, growth factor delivery in situ is far from trivial and, in many cases, the necessary growth factors are not approved for clinical use. Here we used a BMP-2 and a TGF-β1 reporter cell line to screen a library of 1280 Food and Drug Administration–approved small molecules and identify modulators of both signaling pathways. We identified four compounds capable of modulating BMP and TGF signaling on primary human tendon–derived cells (huTCs) and describe their effects on proliferation and differentiation of these cells.

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 81-89 ◽  
Author(s):  
Jing Liu ◽  
Tan Deng ◽  
Yaxin Wang ◽  
Mengmeng Zhang ◽  
Guannan Zhu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Collagen I ◽  
Smad Pathway ◽  
Smad Signaling ◽  
Intestinal Fibrosis ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Background: Intestinal fibrosis is the major complication of Crohn’s disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. Methods: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-β1 (TGF-β1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-β/Smad pathway. Results: The results showed that the concentration of CA was 12.5, 25, 50 μmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-β/Smad signaling pathway. Conclusion: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-β/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-β1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-β/Smad pathway.

scholarly journals Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy

2018 ◽  
Vol 132 (21) ◽  
pp. 2299-2322 ◽  
Author(s):  
Jinfang Bao ◽  
Yingfeng Shi ◽  
Min Tao ◽  
Na Liu ◽  
Shougang Zhuang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Growth Factor Receptor ◽  
Nuclear Factor Κb ◽  
Transforming Growth Factor Β1 ◽  
Renal Tissue ◽  
Tgf Β1

Autophagy has been identified as a cellular process of bulk degradation of cytoplasmic components and its persistent activation is critically involved in the renal damage induced by ureteral obstruction. However, the role and underlying mechanisms of autophagy in hyperuricemic nephropathy (HN) remain unknown. In the present study, we observed that inhibition of autophagy by 3-methyladenine (3-MA) abolished uric acid-induced differentiation of renal fibroblasts to myofibroblasts and activation of transforming growth factor-β1 (TGF-β1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways in cultured renal interstitial fibroblasts. Treatment with 3-MA also abrogated the development of HN in vivo as evidenced by improving renal function, preserving renal tissue architecture, reducing the number of autophagic vacuoles, and decreasing microalbuminuria. Moreover, 3-MA was effective in attenuating renal deposition of extracellular matrix (ECM) proteins and expression of α-smooth muscle actin (α-SMA) and reducing renal epithelial cells arrested at the G2/M phase of cell cycle. Injury to the kidney resulted in increased expression of TGF-β1 and TGFβ receptor I, phosphorylation of Smad3 and TGF-β-activated kinase 1 (TAK1), and activation of multiple cell signaling pathways associated with renal fibrogenesis, including Wnt, Notch, EGFR, and nuclear factor-κB (NF-κB). 3-MA treatment remarkably inhibited all these responses. In addition, 3-MA effectively suppressed infiltration of macrophages and lymphocytes as well as release of multiple profibrogenic cytokines/chemokines in the injured kidney. Collectively, these findings indicate that hyperuricemia-induced autophagy is critically involved in the activation of renal fibroblasts and development of renal fibrosis and suggest that inhibition of autophagy may represent a potential therapeutic strategy for HN.

Transforming growth factor-β1 induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways

2018 ◽  
Vol 96 (5) ◽  
pp. 527-534 ◽  
Author(s):  
Brice Ongali ◽  
Nektaria Nicolakakis ◽  
Xin-Kang Tong ◽  
Clotilde Lecrux ◽  
Hans Imboden ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cerebrovascular Reactivity ◽  
Cerebrovascular Dysfunction ◽  
Tgf Β1

Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only subtle cognitive deficits. TGF-β1 may exert part of its deleterious effects through interactions with angiotensin II (AngII) type 1 receptor (AT1R) signaling pathways. We test such interactions in the brain and cerebral vessels of TGF mice by measuring cerebrovascular reactivity, levels of protein markers of vascular fibrosis, nitric oxide synthase activity, astrogliosis, and mnemonic performance in mice treated (6 months) with the AT1R blocker losartan (10 mg/kg per day) or the angiotensin converting enzyme inhibitor enalapril (3 mg/kg per day). Both treatments restored the severely impaired cerebrovascular reactivity to acetylcholine, calcitonin gene-related peptide, endothelin-1, and the baseline availability of nitric oxide in aged TGF mice. Losartan, but not enalapril, significantly reduced astrogliosis and cerebrovascular levels of profibrotic protein connective tissue growth factor while raising levels of antifibrotic enzyme matrix metallopeptidase-9. Memory was unaffected by aging and treatments. The results suggest a pivotal role for AngII in TGF-β1-induced cerebrovascular dysfunction and neuroinflammation through AT1R-mediated mechanisms. Further, they suggest that AngII blockers could be appropriate against vasculopathies and astrogliosis associated with AD and VCID.

scholarly journals Transforming growth factor-β1 impairs CFTR-mediated anion secretion across cultured porcine vas deferens epithelial monolayer via the p38 MAPK pathway

2013 ◽  
Vol 305 (8) ◽  
pp. C867-C876 ◽  
Author(s):  
Sheng Yi ◽  
Fernando Pierucci-Alves ◽  
Bruce D. Schultz
Keyword(s):  
Cystic Fibrosis ◽  
Growth Factor ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Vas Deferens ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Transforming Growth Factor Β1 ◽  
Anion Secretion ◽  
Tgf Β1

The goal of this study was to determine whether transforming growth factor-β1 (TGF-β1) affects epithelial cells lining the vas deferens, an organ that is universally affected in cystic fibrosis male patients. In PVD9902 cells, which are derived from porcine vas deferens epithelium, TGF-β1 exposure significantly reduced short-circuit current ( Isc) stimulated by forskolin or a cell membrane-permeant cAMP analog, 8-pCPT-cAMP, suggesting that TGF-β1 affects targets of the cAMP signaling pathway. Electrophysiological results indicated that TGF-β1 reduces the magnitude of current inhibited by cystic fibrosis transmembrane conductance regulator (CFTR) channel blockers. Real-time RT-PCR revealed that TGF-β1 downregulates the abundance of mRNA coding for CFTR, while biotinylation and Western blot showed that TGF-β1 reduces both total CFTR and apical cell surface CFTR abundance. These results suggest that TGF-β1 causes a reduction in CFTR expression, which limits CFTR-mediated anion secretion. TGF-β1-associated attenuation of anion secretion was abrogated by SB431542, a TGF-β1 receptor I inhibitor. Signaling pathway studies showed that the effect of TGF-β1 on Isc was reduced by SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK). TGF-β1 exposure also increased the amount of phospho-p38 MAPK substantially. In addition, anisomycin, a p38 MAPK activator, mimicked the effect of TGF-β1, which further suggests that TGF-β1 affects PVD9902 cells through a p38 MAPK pathway. These observations suggest that TGF-β1, via TGF-β1 receptor I and p38 MAPK signaling, reduces CFTR expression to impair CFTR-mediated anion secretion, which would likely compound the effects associated with mild CFTR mutations and ultimately would compromise male fertility.

Rho kinase mediates transforming growth factor-β1-induced vasculogenic mimicry formation: involvement of the epithelial–mesenchymal transition and cancer stemness activity

2020 ◽  
Vol 52 (4) ◽  
pp. 411-420 ◽  
Author(s):  
Xue Zhang ◽  
Jigang Zhang ◽  
Heming Zhou ◽  
Gaolin Liu ◽  
Qin Li
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Vasculogenic Mimicry ◽  
Rho Kinase ◽  
Transforming Growth Factor Β1 ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, has been identified in several malignant tumors, including hepatocellular carcinoma (HCC). Rho kinase (ROCK) plays an important role in various types of cancers. However, whether ROCK participates in transforming growth factor-β1 (TGF-β1)-induced VM formation is unclear. Here, we evaluated the role of ROCK in TGF-β1-induced VM formation in HCC. Our findings showed that the TGF-β1/ROCK signaling pathway is involved in VM formation by inducing the epithelial–mesenchymal transition. Furthermore, TGF-β1 and ROCK were found to play distinct roles in the cancer stem cell phenotype during VM formation. These results provide insights into potential antitumor therapies for inhibiting VM by targeting the TGF-β1/ROCK signaling pathway in HCC.

scholarly journals Mutant p53 Attenuates the SMAD-Dependent Transforming Growth Factor β1 (TGF-β1) Signaling Pathway by Repressing the Expression of TGF-β Receptor Type II

2007 ◽  
Vol 27 (23) ◽  
pp. 8228-8242 ◽  
Author(s):  
Eyal Kalo ◽  
Yosef Buganim ◽  
Keren E. Shapira ◽  
Hilla Besserglick ◽  
Naomi Goldfinger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Receptor Type ◽  
Mutant P53 ◽  
Type Ii ◽  
Wild Type ◽  
Gain Of Function ◽  
Β Receptor ◽  
Tgf Β1

ABSTRACT Both transforming growth factor beta (TGF-β) and p53 have been shown to control normal cell growth. Acquired mutations either in the TGF-β signaling pathway or in the p53 protein were shown to induce malignant transformation. Recently, cross talk between wild-type p53 and the TGF-β pathway was observed. The notion that mutant p53 interferes with the wild-type p53-induced pathway and acts by a “gain-of-function” mechanism prompted us to investigate the effect of mutant p53 on the TGF-β-induced pathway. In this study, we show that cells expressing mutant p53 lost their sensitivity to TGF-β1, as observed by less cell migration and a reduction in wound healing. We found that mutant p53 attenuates TGF-β1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus. Furthermore, we found that mutant p53 attenuates the TGF-β1-induced transcription activity of SMAD2/3 proteins. In searching for the mechanism that underlies this attenuation, we found that mutant p53 reduces the expression of TGF-β receptor type II. These data provide important insights into the molecular mechanisms that underlie mutant p53 “gain of function” pertaining to the TGF-β signaling pathway.

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