IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Title
IGFBP5 mediates high glucose-induced cardiac fibroblast activation
Author(s)
박소영송승은김용운김종연이동협김재룡
Keywords
FACTOR-BINDING PROTEIN-5; INTESTINAL SMOOTH-MUSCLE; ENDOTHELIAL-CELLS; NEUROBLASTOMA-CELLS; PULMONARY-FIBROSIS; DOWN-REGULATION; MESSENGER-RNAS; DIABETIC-RATS; IN-VITRO; INSULIN
Issue Date
201306
Publisher
BIOSCIENTIFICA LTD
Citation
JOURNAL OF MOLECULAR ENDOCRINOLOGY, v.50, no.3, pp.291 - 303
Abstract
This study examined whether IGF-binding protein 5 (IGFBP5) is involved in the high glucose-induced deteriorating effects in cardiac cells. Cardiac fibroblasts and cardiomyocytes were isolated from the hearts of 1- to 3-day-old Sprague Dawley rats. Treatment of fibroblasts with 25 mM glucose increased the number of cells and the mRNA levels of collagen III, matrix metalloproteinase 2 (MMP2), and MMP9. High glucose increased ERK1/2 activity, and the ERK1/2 inhibitor PD98059 suppressed high glucose-mediated fibroblast proliferation and increased collagen III mRNA levels. Whereas high glucose increased both mRNA and protein levels of IGFBP5 in fibroblasts, high glucose did not affect IGFBP5 protein levels in cardiomyocytes. The high glucose-induced increase in IGFBP5 protein levels was inhibited by PD98059 in fibroblasts. While recombinant IGFBP5 increased ERK phosphorylation, cell proliferation, and the mRNA levels of collagen III, MMP2, and MMP9 in fibroblasts, IGFBP5 increased c-Jun N-terminal kinase phosphorylation and induced apoptosis in cardiomyocytes. The knockdown of IGFBP5 inhibited high glucose-induced cell proliferation and collagen III mRNA levels in fibroblasts. Although high glucose increased IGF1 levels, IGF1 did not increase IGFBP5 levels in fibroblasts. The hearts of Otsuka Long-Evans Tokushima Fatty rats and the cardiac fibroblasts of streptozotocin-induced diabetic rats showed increased IGFBP5 expression. These results suggest that IGFBP5 mediates high glucose-induced profibrotic effects in cardiac fibroblasts.
URI
http://hdl.handle.net/YU.REPOSITORY/29915http://dx.doi.org/10.1530/JME-12-0194
ISSN
0952-5041
Appears in Collections:
의과대학 > 생리학교실 > Articles
의과대학 > 영상의학과학교실 > Articles
의과대학 > 흉부외과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
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