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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제22권 제2호
- 발행연도
- 2018.3
- 수록면
- 193 - 201 (9page)
- DOI
- https://doi.org/10.4196/kjpp.2018.22.2.193
이용수
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Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs.
Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.
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참고문헌 (29)
참고문헌 신청
Andreea SI / 2008 / AGEs and glucose levels modulate type I and III procollagen mRNA synthesis in dermal fibroblasts cells culture / Exp Diabetes Res 2008:473603
Makita Z / 1994 / Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure / Lancet 343:1519~1522
Cooper ME / 2004 / Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease / Am J Hypertens 17:31S~38S
Reddy GK / 2004 / AGE-related cross-linking of collagen is associated with aortic wall matrix stiffness in the pathogenesis of drug-induced diabetes in rats / Microvasc Res 68:132~142
Throckmorton DC / 1995 / PDGF and TGF-beta mediate collagen production by mesangial cells exposed to advanced glycosylation end products / Kidney Int 48:111~117
Makita Z / 1994 / Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure / Lancet 343:1519~1522
Cooper ME / 2004 / Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease / Am J Hypertens 17:31S~38S
Reddy GK / 2004 / AGE-related cross-linking of collagen is associated with aortic wall matrix stiffness in the pathogenesis of drug-induced diabetes in rats / Microvasc Res 68:132~142
Throckmorton DC / 1995 / PDGF and TGF-beta mediate collagen production by mesangial cells exposed to advanced glycosylation end products / Kidney Int 48:111~117
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