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The role of hyperglycemia on cardiac fibroblast function: proliferation and ERK activation
Author(s) -
Shamhart Patricia E.,
Luther Daniel J.,
Raman Priya,
Meszaros J Gary
Publication year - 2010
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.24.1_supplement.816.6
Subject(s) - mapk/erk pathway , endocrinology , medicine , fibroblast , myofibroblast , phosphorylation , angiotensin ii , basal (medicine) , extracellular matrix , diabetes mellitus , microbiology and biotechnology , chemistry , in vitro , biology , fibrosis , receptor , biochemistry
Cardiac fibroblasts (CFs) are critical mediators of remodeling and upon activation secrete extracellular matrix, proliferate, migrate, and differentiate to the hypersecretory myofibroblast phenotype. Myofibroblasts are significant regulators of wound healing, a process that is compromised in diabetic patients. The MAPK pathway is a classical proliferation pathway in many cell types including CFs as previously reported by our laboratory. The goal of this study was to determine the influence of hyperglycemia on CFs with a particular focus on proliferation and ERK activation. Our previously published study reported that fibroblasts isolated from 6 week streptozotocin‐induced type 1 diabetic hearts had a 15.6% higher proliferation rate versus those from control hearts. In this study we utilized hyperglycemic media (25 mmol/l) to mimic diabetes in vitro . Surprising, short term hyperglycemia significantly attenuated basal ERK activation: ERK phosphorylation decreased to 14.8 ± 4.8% control in CFs treated for 20 minutes with high glucose and 6.4 ± 2.7% control at 1 hour. We also observed that short term high glucose incubation slightly attenuated angiotensin II induced ERK phosphorylation. These data suggest high glucose attenuates basal ERK activation and hyperglycemia‐induced CF proliferation may be independent of the classical MAPK pathway.