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Myofibroblast in the ligamentum flavum hypertrophic activity

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Title
Myofibroblast in the ligamentum flavum hypertrophic activity
Author(s)
Junseok W. Hur; Taegeun Bae; Sunghyeok Ye; Joo-Hyun Kim; Sunhye Lee; Kyoungmi Kim; Seung-Hwan Lee; Jin-Soo Kim; Jang-Bo Lee; Tai-Hyoung Cho; Jung-Yul Park; Junho K. Hur
Subject
Ligamentum flavum, ; Hypertrophy, ; Myofibroblasts, ; Alpha-smooth muscle actin, ; Transforming growth factor beta1
Publication Date
2017-08
Journal
EUROPEAN SPINE JOURNAL, v.26, no.8, pp.2021 - 2030
Publisher
SPRINGER
Abstract
Majority of the previous studies compared lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) patients for analyses of LFH. However, the separation of normal/hypertrophied LF has often been ambiguous and the severity of hypertrophic activity differed. Here, we present a novel analysis scheme for LFH in which myofibroblast is proposed as a major etiological factor for LFH study. Seventy-one LF patient tissue samples were used for this study. Initially, mRNA levels of the samples were assessed by qRT-PCR: angiopoietin-like protein-2 (ANGPTL2), transforming growth factor-beta1 (TGF-beta 1), vascular endothelial growth factor (VEGF), interleukin-6, collagen-1, 3, 4, 5, and 11, and elastin. Myofibroblasts were detected by immune stain using alpha-smooth muscle actin (alpha SMA) as a marker. To study the myofibroblast in TGF-beta pathway, LF tissues were analyzed for protein levels of alpha SMA/TGF-beta 1 by Western blot. In addition, from LF cells cultured with exogenous TGF-beta 1 conditioned medium, expression of alpha SMA/collagen-1 was assessed and the cell morphology was identified. The comparative analysis of mRNA expression levels (LSS vs LDH) failed to show significant differences in TGF-beta 1 (p = 0.08); however, we found a significant positive correlation among ANGPTL2, VEGF, TGF-beta 1, and collagen-1 and 3, which represent common trends in hypertrophic activity (p < 0.05). We detected myofibroblast in the patient samples by alpha SMA staining, and the protein levels of alpha SMA were positively correlated with TGF-beta 1. In LF cell culture, exogenous TGF-beta 1 upregulated alpha SMA/collagen-1 mRNA levels and facilitated trans-differentiation to myofibroblast. We conclude that the transition of fibroblast to myofibroblasts via TGF-beta pathway is a key linker between inflammation and fibrosis in LFH mechanism. (c) Springer-Verlag Berlin Heidelberg 2017
URI
https://pr.ibs.re.kr/handle/8788114/4011
DOI
10.1007/s00586-017-4981-2
ISSN
0940-6719
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
10.1007%2Fs00586-017-4981-2.pdfDownload

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