NDLI: Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-{beta} activity in vascular smooth muscle cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Shuxia Lincoln, Thomas M. Murphy-Ullrich, Joanne E.
Description	Country affiliation: United States Author Affiliation: Wang S ( Univ. of Kentucky, Lexington, 40536, USA. swang7@uky.edu)
Abstract	Diabetes is a major predictor of in-stent restenosis, which is associated with fibroproliferative remodeling of the vascular wall due to increased transforming growth factor-beta (TGF-beta) action. It is well established that thrombospondin1 (TSP1) is a major regulator of TGF-beta activation in renal and cardiac complications of diabetes. However, the role of the TSP1-TGF-beta pathway in macrovascular diabetic complications, including restenosis, has not been addressed. In mesangial cells, high glucose concentrations depress protein kinase G (PKG) activity, but not PKG-I protein, thereby downregulating transcriptional repression of TSP1. Previously, we showed that high glucose downregulates PKG-I protein expression by vascular smooth muscle cells (VSMCs) through altered NADPH oxidase signaling. In the present study, we investigated whether high glucose regulation of PKG protein and activity in VSMCs similarly regulates TSP1 expression and downstream TGF-beta activity. These studies showed that high glucose stimulates both TSP1 expression and TGF-beta bioactivity in primary murine aortic smooth muscle cells (VSMCs). TSP1 is responsible for the increased TGF-beta bioactivity under high glucose conditions, because treatment with anti-TSP1 antibody, small interfering RNA-TSP1, or an inhibitory peptide blocked glucose-mediated increases in TGF-beta activity and extracellular matrix protein (fibronectin) expression. Overexpression of constitutively active PKG, but not the PKG-I protein, inhibited glucose-induced TSP1 expression and TGF-beta bioactivity, suggesting that PKG protein expression is insufficient to regulate TSP1 expression. Together, these data establish that glucose-mediated downregulation of PKG levels stimulates TSP1 expression and enhances TGF-beta activity and matrix protein expression, which can contribute to vascular remodeling in diabetes.
File Format	HTM / HTML
ISSN	03636143
e-ISSN	15221563
DOI	10.1152/ajpcell.00330.2009
Journal	American Journal of Physiology - Cell Physiology
Issue Number	5
Volume Number	298
Language	English
Publisher	American Physiological Society
Publisher Date	2010-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Cyclic Gmp-dependent Protein Kinases Metabolism Glucose Pharmacology Muscle, Smooth, Vascular Cytology Myocytes, Smooth Muscle Thrombospondin 1 Transforming Growth Factor Beta Animals Cells, Cultured Genetics Diabetes Mellitus Down-regulation Extracellular Matrix Proteins Gene Expression Regulation, Enzymologic Mice Mice, Inbred C57bl Nadph Oxidase Rna, Messenger Time Factors Up-regulation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-β activity in vascular smooth muscle cells

Upregulation of thrombospondin-1 expression by leptin in vascular smooth muscle cells via JAK2- and MAPK-dependent pathways.

Glycosylation Mediates Up-regulation of a Potent Antiangiogenic and Proatherogenic Protein, Thrombospondin-1, by Glucose in Vascular Smooth Muscle Cells

NADPH oxidase 4 mediates TGF-ß-induced smooth muscle -actin via p38MAPK and serum response factor.

Transforming growth factor beta 1 and hyaluronan oligomers synergistically enhance elastin matrix regeneration by vascular smooth muscle cells.

Advanced glycation end products-induced vascular calcification is mediated by oxidative stress: functional roles of NAD(P)H-oxidase.

Steroid-sensitive gene 1 is a novel cyclic GMP-dependent protein kinase I substrate in vascular smooth muscle cells.

Protein tyrosine phosphatase PTPepsilonM negatively regulates PDGF beta-receptor signaling induced by high glucose and PDGF in vascular smooth muscle cells.

Fibronectin upregulates cGMP-dependent protein kinase type Iß through C/EBP transcription factor activation in contractile cells.

Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-{beta} activity in vascular smooth muscle cells.

Similar Documents

Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-β activity in vascular smooth muscle cells

Upregulation of thrombospondin-1 expression by leptin in vascular smooth muscle cells via JAK2- and MAPK-dependent pathways.

Glycosylation Mediates Up-regulation of a Potent Antiangiogenic and Proatherogenic Protein, Thrombospondin-1, by Glucose in Vascular Smooth Muscle Cells

NADPH oxidase 4 mediates TGF-ß-induced smooth muscle -actin via p38MAPK and serum response factor.

Transforming growth factor beta 1 and hyaluronan oligomers synergistically enhance elastin matrix regeneration by vascular smooth muscle cells.

Advanced glycation end products-induced vascular calcification is mediated by oxidative stress: functional roles of NAD(P)H-oxidase.

Steroid-sensitive gene 1 is a novel cyclic GMP-dependent protein kinase I substrate in vascular smooth muscle cells.

Protein tyrosine phosphatase PTPepsilonM negatively regulates PDGF beta-receptor signaling induced by high glucose and PDGF in vascular smooth muscle cells.

Fibronectin upregulates cGMP-dependent protein kinase type Iß through C/EBP transcription factor activation in contractile cells.

Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-{beta} activity in vascular smooth muscle cells.