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Autophagy in phenoconversion of differentiated and undifferentiated fibroblasts
Author(s) -
Gupta Shivika,
Kavosh Morvarid,
Chen ShuRu,
Ghavami Saeid,
Rattan Sunil,
Klonisch Thomas,
Dixon Ian
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1129.14
Subject(s) - autophagy , atg5 , myofibroblast , fibroblast , fibronectin , microbiology and biotechnology , chemistry , western blot , cancer research , biology , pathology , apoptosis , fibrosis , medicine , extracellular matrix , in vitro , biochemistry , gene
Cardiac fibroblasts phenoconvert to hypersecretory myofibroblasts and deposit matrix resulting in cardiac fibrosis and autophagy that is associated to fibroproliferative events. Autophagy inhibition was studied in both primary (P0) rat cardiac fibroblasts (PF) and mouse embryonic fibroblasts (MEF). Autophagy was inhibited in PF using Baf‐A1 or 3‐MA while MEF ATG3 and ATG5 KO were also used. Western blot analysis, Immunofluorescence, and transmission electron microscopy were used to investigate autophagy and fibroblast to myofibroblast phenoconversion. α‐SMA and ED‐A fibronectin were assessed as phenoconversion markers. Inhibition of autophagy was revealed by punctate LC3‐II staining and double membrane autophagosomes in combination with decreased myofibroblast markers in PF vs. controls. Inhibition of autolysosome formation and accumulation of autophagosomes were found in Baf‐A1 treated cells. Conversely, ATG3 and ATG5 KO MEF cells showed increased myofibroblast markers vs. WT controls. Increased α‐SMA was seen in MEF ATG3 and ATG5 KO vs. controls while inhibition of autophagy in PFs showed diminished myofibroblastic phenotype vs. controls. A link between fibroblast phenoconversion and autophagy is established. This effect is dependent on cell type eg, PFs vs. MEFs. This finding illustrates that autophagy functions in a variable manner in differentiated vs. non‐differentiated fibroblasts.