• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권2호
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• pp.63-69
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• 2017

Nuclear factor I-C (NFI-C) plays a pivotal role in various cellular processes such as odontoblast and osteoblast differentiation. Nfic-deficient mice showed abnormal tooth and bone formation. The transplantation of Nfic-expressing mouse bone marrow stromal cells rescued the impaired bone formation in $Nfic^{-/-}$ mice. Studies suggest that NFI-C regulate osteogenesis and dentinogenesis in concert with several factors including transforming growth factor-${\beta}1$, $Kr{\ddot{u}}ppel$-like factor 4, and ${\beta}$-catenin. This review will focus on the function of NFI-C during tooth and bone formation and on the relevant pathways that involve NFI-C.

• Molecules and Cells
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• 제37권3호
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• pp.196-201
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• 2014

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative vascular cells. Clinically, PAH leads to increased pulmonary arterial pressure and subsequent right ventricular failure. Existing therapies have improved the outcome but mortality still remains exceedingly high. There is emerging evidence that the seven-transmembrane G-protein coupled receptor APJ and its cognate endogenous ligand apelin are important in the maintenance of pulmonary vascular homeostasis through the targeting of critical mediators, such as Kr$\ddot{u}$ppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and microRNAs (miRNAs). Disruption of this pathway plays a major part in the pathogenesis of PAH. Given its role in the maintenance of pulmonary vascular homeostasis, the apelin-APJ pathway is a potential target for PAH therapy. This review highlights the current state in the understanding of the apelin-APJ axis related to PAH and discusses the therapeutic potential of this signaling pathway as a novel paradigm of PAH therapy.

• 한국식품과학회지
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• 제50권6호
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• pp.688-696
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• 2018

본 연구에서는 홍삼 사포닌 분획(SF)으로부터 진세노사이드의 조성을 분석하고 지방세포의 분화 및 지방축적에 대한 효과를 측정하였다. SF는 지방분화인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$의 단백질 양을 억제함으로써 지방분화 동안 효과적으로 지방축적을 억제하였으며 주로 지방분화 초기시점부터 지방분화 초기인자인 $C/EBP{\beta}$, KLF2의 조절작용을 통해 지방축적을 억제하는 것으로 관찰되었다. SF는 또한 지방분화 동안 생성되는 ROS의 생성을 효과적으로 억제하였는데 이는 SF가 산화방지 시스템인 Nrf2/Keap1 경로를 활성화하기 때문으로 판단되며 특히 Nrf2의 핵 내로의 진입을 활성화 함으로써 Nrf2의 타겟 산화방지 분자들인 HO-1, NQO1의 발현을 촉진하였다. 이는 지방분화 동안 SF의 지방축적 억제 효과가 Nrf2의 활성화와 밀접하게 관련이 있음을 보여준다.

• Experimental and Molecular Medicine
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• 제51권2호
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• pp.9.1-9.10
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• 2019

Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of ${\alpha}-SMA^+/PCNA^+$ cells was increased in the kidney cortex of db/db mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of $p27^{Kip1}$ was decreased. The expression of $Kr{\ddot{u}}ppel$-like factor 5 (KLF5) was upregulated in the kidney cortex of db/db mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of db/db mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.

• 한국수산과학회지
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• 제48권4호
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• pp.439-446
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• 2015

Inflammation is a protective response to infection or injury. However, prolonged inflammation can contribute to the pathogenesis of many diseases, such as cancer, diabetes, arthritis, atherosclerosis, and Alzheimer's disease. Recent studies have shown that activated macrophages, inflammatory effector cells, can react to tissue insults in a polarized manner, in which their phenotypes are polarized into two major subtypes, categorized as M1 or M2. Classical M1 activation involves the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$, and free radicals, while M2 or alternative activation is an anti-inflammatory phenotype involved in homeostatic processes, such as wound healing, debris scavenging, and the dampening of inflammation via the production of very low levels of pro-inflammatory cytokines and high levels of anti-inflammatory mediators, including IL-10. As part of our ongoing effort to isolate anti-inflammatory compounds from seaweeds, we investigated the effects of phlorotannins isolated from the brown alga Ecklonia stolonifera on macrophage polarization. Mouse peritoneal macrophages were treated with various concentrations of the extracts, and real-time RT-PCR analyses were performed to examine the expression of polarization markers: IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ for M1 and arginase-1, peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, found inflammatory zone-1 (Fizz-1), chitinase 3-like 3 (Ym1), and$Kr{\ddot{u}}ppel$-like factor 4 (Klf-4) for M2. The pretreatment of cells with eckol, dieckol, and phlorofucofuroeckol-A (PFF-A), isolated from the ethyl acetate fraction of E. stolonifera ethanolic extract, potentiated the anti-inflammatory M2 phenotype of the macrophages. These results indicate that phlorotannins derived from E. stolonifera can be used to enrich macrophages with markers of the M2 anti-inflammatory state.