Polymerase delta-interacting protein 2 regulates collagen accumulation via activation of the Akt/mTOR pathway in vascular smooth muscle cells

Journal of Molecular and Cellular Cardiology
Masakazu FujiiKathy K Griendling

Abstract

Polymerase delta interacting protein 2 (Poldip2) has previously been implicated in migration, proliferation and extracellular matrix (ECM) production in vascular smooth muscle cells. To better understand the role of Poldip2 in ECM regulation, we investigated the mechanism responsible for collagen I accumulation in Poldip2(+/-) mouse aortic smooth muscle cells (MASMs). Protein degradation and protein synthesis pathways were investigated. Depletion of Poldip2 had no effect on proteasome activity, but caused a partial reduction in autophagic flux. However, the rate of collagen I degradation was increased in Poldip2(+/-) vs. Poldip2(+/+) MASMs. Conversely, activation of the PI3K/Akt/mTOR signaling pathway, involved in regulation of protein synthesis, was significantly elevated in Poldip2(+/-) MASMs as was β1-integrin expression. Suppressing mTOR signaling using Akt inhibitor or rapamycin and reducing β1-integrin expression using siRNA prevented the increase in collagen I production. While collagen I and fibronectin were increased in Poldip2(+/-) MASMs, overall protein synthesis was not different from that in Poldip2(+/)(+)MASMs, suggesting selectivity of Poldip2 for ECM proteins. Poldip2(+/-) MASMs exhibit higher β1-integrin expres...Continue Reading

References

Jun 29, 2000·Annual Review of Biochemistry·A C GingrasN Sonenberg
Sep 20, 2000·The Journal of Cell Biology·Y KamadaY Ohsumi
Sep 23, 2000·Nature·A J Lusis
Apr 12, 2001·Genes & Development·A C GingrasN Sonenberg
Oct 13, 2004·Free Radical Biology & Medicine·Ibrahim R HannaKathy K Griendling
Dec 30, 2004·Nature Genetics·Ken InokiKun-Liang Guan
Nov 4, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Roza E ClempusKathy K Griendling
Sep 22, 2007·Current Opinion in Lipidology·Prediman K Shah
Apr 30, 2008·Methods : a Companion to Methods in Enzymology·David R EyreJiann-Jiu Wu
Apr 30, 2008·Methods : a Companion to Methods in Enzymology·Vincent Everts, Dave J Buttle
Jul 4, 2009·Circulation Research·Alicia N LyleKathy K Griendling
Jan 9, 2010·Current Opinion in Cell Biology·Noboru Mizushima
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine
Feb 18, 2010·Proceedings of the American Thoracic Society·Eloy Bejarano, Ana Maria Cuervo
May 12, 2010·Molecular and Cellular Biology·Ru-Feng WuLance S Terada
Jun 11, 2010·Annual Review of Biochemistry·Marc Robert FabianWitold Filipowicz
Jul 14, 2010·Autophagy·Ru Feng Wu, Lance S Terada
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
May 17, 2011·Annual Review of Cell and Developmental Biology·Birgit Leitinger
Jan 25, 2012·The Journal of Clinical Investigation·Lars MaegdefesselPhilip S Tsao
Feb 24, 2012·Nature Reviews. Molecular Cell Biology·Bart VanhaesebroeckPhillip Hawkins
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
May 1, 2012·Cell·Margaret S Ebert, Phillip A Sharp
Jan 22, 2013·The Journal of Biological Chemistry·Hsueh-Liang FuRafael Fridman
Feb 15, 2013·The New England Journal of Medicine·Augustine M K ChoiBeth Levine
May 10, 2013·The New England Journal of Medicine·Augustine M K ChoiBeth Levine
Jun 19, 2013·The American Journal of Pathology·Chaoyong HeZhonglin Xie
Jul 5, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Roy L SutliffBernard Lassègue
Aug 7, 2013·Toxicology and Applied Pharmacology·Arya SobhakumariAndrean L Simons
Nov 16, 2013·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Sebastiano SciarrettaJunichi Sadoshima
May 24, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Angélica M AmansoKathy K Griendling
Jun 7, 2014·Circulation Research·Jacob Fog BentzonErling Falk
Sep 10, 2014·Circulation Research·Anna ZampetakiManuel Mayr

❮ Previous
Next ❯

Citations

Mar 8, 2016·Journal of Molecular and Cellular Cardiology·Shouji MatsushimaJunichi Sadoshima
Dec 6, 2016·Journal of Cellular Biochemistry·Sakie KatsumuraYoichi Ezura
Jun 3, 2017·Journal of Cardiovascular Pharmacology·Marina S HernandesKathy K Griendling
Feb 20, 2019·International Journal of Molecular Sciences·Lei FangMichael Roth
Feb 7, 2019·American Journal of Physiology. Cell Physiology·Lauren Parker HuffKathy K Griendling
Nov 1, 2018·Physiological Reviews·Jesús TejeroMark T Gladwin
Dec 21, 2021·PloS One·Bernard LassègueKathy K Griendling
Dec 14, 2021·PLoS Computational Biology·Ana C EstradaJay D Humphrey

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.