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.
['Gubbiotti|Maria A|MA|', 'Neill|Thomas|T|', 'Frey|Helena|H|', 'Schaefer|Liliana|L|', 'Iozzo|Renato V|RV|']
D000818:Animals D001343:Autophagy D058578:Biglycan D058575:Decorin D005109:Extracellular Matrix D005215:Fasting D005260:Female D005786:Gene Expression Regulation D017930:Genes, Reporter D049452:Green Fluorescent Proteins D006801:Humans D008156:Luciferases D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008869:Microtubule-Associated Proteins D009206:Myocardium D041681:NIH 3T3 Cells D011993:Recombinant Fusion Proteins D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases
Extracellular matrix mTOR Cardiac muscle LC3 Macroautophagy SQSTM1 Small leucine-rich proteoglycan