Reduction of fibroblast size/mechanical force down-regulates TGF-β type II receptor: implications for human skin aging

Aging Cell
Gary J FisherTaihao Quan

Abstract

The structural integrity of human skin is largely dependent on the quality of the dermal extracellular matrix (ECM), which is produced, organized, and maintained by dermal fibroblasts. Normally, fibroblasts attach to the ECM and thereby achieve stretched, elongated morphology. A prominent characteristic of dermal fibroblasts in aged skin is reduced size, with decreased elongation and a more rounded, collapsed morphology. Here, we show that reduced size of fibroblasts in mechanically unrestrained three-dimensional collagen lattices coincides with reduced mechanical force, measured by atomic force microscopy. Reduced size/mechanical force specifically down-regulates TGF-β type II receptor (TβRII) and thus impairs TGF-β/Smad signaling pathway. Both TβRII mRNA and protein were decreased, resulting in 90% loss of TGF-β binding to fibroblasts. Down-regulation of TβRII was associated with significantly decreased phosphorylation, DNA-binding, and transcriptional activity of its key downstream effector Smad3 and reduced expression of Smad3-regulated essential ECM components type I collagen, fibronectin, and connective tissue growth factor (CTGF/CCN2). Restoration of TβRII significantly increased TGF-β induction of Smad3 phosphorylation ...Continue Reading

References

Jul 27, 2001·The Journal of Biological Chemistry·D KesslerB Eckes
Feb 14, 2002·The Journal of Investigative Dermatology·Franck Verrecchia, Alain Mauviel
Jun 4, 2004·The Journal of Investigative Dermatology·James VaraniJohn J Voorhees
Nov 19, 2005·Science·Dennis E DischerYu-Li Wang
Jun 5, 2007·Journal of Cellular Biochemistry·Randall S Gieni, Michael J Hendzel
Mar 13, 2008·Science Signaling·Rebecca G Wells, Dennis E Discher
May 21, 2008·Archives of Dermatology·Gary J FisherJohn J Voorhees
Jun 3, 2008·Trends in Cell Biology·Richard K Assoian, Eric A Klein
Jan 24, 2009·Nature Reviews. Cancer·Darci T ButcherValerie M Weaver
Feb 17, 2009·Current Opinion in Cell Biology·Viola Vogel, Michael P Sheetz
Jun 23, 2009·Biochimica Et Biophysica Acta·Dirk PohlersGunter Wolf
Jul 7, 2009·Annual Review of Cell and Developmental Biology·Frederick Grinnell, W Matthew Petroll
Apr 24, 2010·Nature Reviews. Molecular Cell Biology·Eric N Olson, Alfred Nordheim
Dec 22, 2010·Journal of Cell Science·Paul A Janmey, R Tyler Miller
Dec 25, 2010·Connective Tissue Research·J P R O OrgelO Antipova
Jun 10, 2011·Nature·Sirio DupontStefano Piccolo
Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Joan Massagué
Apr 17, 2013·Biomaterials·Isabel HoppKrasimir Vasilev
Jun 4, 2013·Nature Cell Biology·Ori MallerValerie M Weaver
Aug 24, 2013·Differentiation; Research in Biological Diversity·Paul A JanmeyChristopher A McCulloch
Oct 9, 2013·Annual Review of Cell and Developmental Biology·Tadanori MammotoDonald E Ingber
Aug 16, 2014·Current Biology : CB·Amnon BuxboimDennis E Discher
Oct 22, 2014·The Journal of Cell Biology·Franco KlingbergBoris Hinz
Oct 31, 2014·Nature Reviews. Molecular Cell Biology·Jay D HumphreyMartin A Schwartz
Oct 31, 2014·Nature Reviews. Molecular Cell Biology·Thomas IskratschMichael P Sheetz
Nov 22, 2014·Nature Reviews. Molecular Cell Biology·Caroline BonnansZena Werb

❮ Previous
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Citations

Jun 5, 2016·International Journal of Cosmetic Science·Y ShaoT Quan
Jan 10, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Asbjorg Osk SnorradottirBirkir Thor Bragason
Nov 20, 2016·Photodermatology, Photoimmunology & Photomedicine·Lawrence Fitzgerald KuklinskiMargaret R Karagas
Jun 12, 2018·Journal of Cellular and Molecular Medicine·Zhaoping QinTaihao Quan
Sep 11, 2017·Journal of Cell Communication and Signaling·Chunji QuanTaihao Quan
Sep 7, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lanju WangYuanfang Ma
Oct 10, 2019·PloS One·Mateus Rennó SantosJames P Lynch
Jan 9, 2018·The American Journal of Surgical Pathology·Yu-Chien KaoCristina R Antonescu
Nov 12, 2019·Immunology·Emma S Chambers, Milica Vukmanovic-Stejic
Jul 25, 2020·Tissue Engineering. Part a·Yuanjia ZhuYi-Ping Joseph Woo
Aug 17, 2020·Biomolecules·Svenja Kleiser, Alexander Nyström
Jun 28, 2020·Journal of Tissue Engineering and Regenerative Medicine·Krzysztof BojanowskiHui Zhao
May 1, 2019·International Journal of Molecular Sciences·Jung-Won ShinKyung-Chan Park
Jul 28, 2017·Cell and Tissue Banking·Jia Xian LawBinti Haji Idrus Ruszymah
May 1, 2020·Proceedings of the National Academy of Sciences of the United States of America·Bibhas RoyG V Shivashankar
Oct 9, 2020·Stem Cells International·Renwang ShengJialin Chen
Nov 25, 2020·Annals of the New York Academy of Sciences·Apratim BajpaiWeiqiang Chen
Dec 29, 2020·The Journal of Investigative Dermatology·Yao Ke, Xiao-Jing Wang
Jan 31, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Zhuonan YuKuo-Kang Liu
Aug 18, 2020·The Journal of Investigative Dermatology·Taihao QuanGary J Fisher
May 29, 2020·Mechanisms of Ageing and Development·Deborah A MilliganCleo L Bishop
Dec 29, 2020·Trends in Cancer·Yi-Wen ShenWei-Dong Zhang
May 28, 2021·Mechanisms of Ageing and Development·Holly N Wilkinson, Matthew J Hardman
Jul 3, 2021·International Journal of Molecular Sciences·Barbara JacczakEwa Totoń
Jun 26, 2020·BioMed Research International·Francesca LombardiBenedetta Cinque
Oct 23, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Ryan J LeiphartPaul A Janmey
Dec 17, 2021·Biological Reviews of the Cambridge Philosophical Society·Anne-France de BengyBérengère Fromy

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Methods Mentioned

BETA
AFM
atomic force microscopy
PCR
laser capture microdissection
electrophoretic
laser
biopsies
protein assay
transfection
fluorescence microscopy

Software Mentioned

image
Storm Molecular Imager
PeakForce
pro plus

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