RRC ID 36007
Author Gubbiotti MA, Neill T, Frey H, Schaefer L, Iozzo RV.
Title Decorin is an autophagy-inducible proteoglycan and is required for proper in vivo autophagy.
Journal Matrix Biol
Abstract 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.
Volume 48
Pages 14-25
Published 2015-10-1
DOI 10.1016/j.matbio.2015.09.001
PII S0945-053X(15)00127-4
PMID 26344480
PMC PMC4661125
MeSH Animals Autophagy / genetics* Biglycan / genetics* Biglycan / metabolism Decorin / deficiency Decorin / genetics* Extracellular Matrix / chemistry Extracellular Matrix / metabolism Fasting / metabolism Female Gene Expression Regulation Genes, Reporter Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Luciferases / genetics Luciferases / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Myocardium / metabolism* NIH 3T3 Cells Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Signal Transduction TOR Serine-Threonine Kinases / genetics* TOR Serine-Threonine Kinases / metabolism
IF 8.572
Times Cited 39
Mice RBRC00806