Decorin is an autophagy-inducible proteoglycan and is required for proper in vivo autophagy.
We have recently discovered that soluble extracellular matrix constituents regulate autophagy via an outside-in signaling pathway. Decorin, a secreted proteoglycan, evokes autophagy in endothelial cells and mitophagy in breast carcinoma cells. However, it is not known whether decorin expression can be regulated by autophagic stimuli such as mTOR inhibition or nutrient deprivation. Thus, we tested whether pro-autophagic stimuli could affect decorin expression in mouse cardiac tissue and whether the absence of decorin could disrupt the in vivo autophagic response. We found that nutrient deprivation induced decorin at the mRNA and protein level in vivo and in vitro, a process regulated at the transcriptional level by inhibiting the canonical mTOR pathway. Moreover, Dcn-/- mice displayed an aberrant response to fasting compared to wild-type mice. Our study establishes a new role for an extracellular matrix proteoglycan and provides a mechanistic role for soluble decorin in regulating a fundamental intracellular catabolic process.
Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Maria A
MA
Gubbiotti
Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Thomas
T
Neill
Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.
Helena
H
Frey
Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.
Liliana
L
Schaefer
Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: renato.iozzo@jefferson.edu.
Renato V
RV
Iozzo
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D058578:Biglycan / Q000235:genetics* / Q000378:metabolism; D058575:Decorin / Q000172:deficiency / Q000235:genetics*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
C546885:Bgn protein, mouse; D058578:Biglycan; C546879:Dcn protein, mouse; D058575:Decorin; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
Cardiac muscle; Extracellular matrix; LC3; Macroautophagy; SQSTM1; Small leucine-rich proteoglycan; mTOR