2. Academic Validation
  3. Pentachloropseudilin Inhibits Transforming Growth Factor-β (TGF-β) Activity by Accelerating Cell-Surface Type II TGF-β Receptor Turnover in Target Cells

Pentachloropseudilin Inhibits Transforming Growth Factor-β (TGF-β) Activity by Accelerating Cell-Surface Type II TGF-β Receptor Turnover in Target Cells

  • Chembiochem. 2018 Apr 16;19(8):851-864. doi: 10.1002/cbic.201700693.
Chih-Ling Chung 1,  Shih-Wei Wang 1,  René Martin 2,  Hans-Joachim Knölker 2,  Yu-Chen Kao 1,  Ming-Hong Lin 3,  Jih-Jung Chen 4,  Yaw-Bin Huang 1 5 6,  Deng-Chyang Wu 7 6,  Chun-Lin Chen 1 8
Affiliations

Affiliations

  • 1 Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, 80424 ROC, Taiwan.
  • 2 Department of Chemistry, Technische Universität Dresden, Bergstrasse 66, 01069, Dresden, Germany.
  • 3 Department of Microbiology and Immunology, Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 80708 ROC, Taiwan.
  • 4 Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, 11221 ROC, Taiwan.
  • 5 Department of Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708 ROC, Taiwan.
  • 6 Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, 80708 ROC, Taiwan.
  • 7 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 80708 ROC, Taiwan.
  • 8 Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung, 80424 ROC, Taiwan.
PMID: 29369495 DOI: 10.1002/cbic.201700693
Abstract

Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was first isolated from Actinoplanes (ATCC33002), and its structure has been confirmed by chemical synthesis. PClP shows broad antimicrobial activity against Gram-negative and Gram-positive bacteria, protozoa, fungi, and yeast. In mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of Myosin 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of Transforming Growth Factor-β (TGF-β)-stimulated signaling. PCIP inhibits TGF-β-stimulated SMAD2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) promoter activation with an IC50 of 0.1 μm in target cells (A549, HepG2, and Mv1Lu cells). In addition, PCIP attenuates TGF-β-stimulated expression of vimentin, N-Cadherin, and fibronectin and, thus, blocks TGF-β-induced epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell-surface labeling and immunoblot analysis indicates that PCIP suppresses TGF-β-stimulated cellular responses by attenuating cell-surface expression of the type II TGF-β Receptor through accelerating caveolae-mediated internalization followed by primarily lysosome-dependent degradation of the receptor, as demonstrated by sucrose density gradient analysis and immune fluorescence staining.

Keywords

growth factors; inhibitors; lipid rafts; organohalogen metabolites; receptor trafficking.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z