• Journal of Life Science
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• v.30 no.11
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• pp.973-982
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• 2020

In this study, we examined inhibition of adipocyte differentiation associated with the administration of camphor, a substance identified in extracts of the flowering plant Chrysanthemum indicum L. (CI). No camphor-mediated cytotoxicity was observed over a period of 1-10 days in studies targeting cells of the 3T3-L1 adipocyte-like line. Experiments that featured siRNA-mediated suppression of the transmembrane proteins Patched (PTCH) and Smoothened (SMO) resulted in inhibition and activation of differentiation, respectively. Interestingly, inhibition of PTCH typically activates SMO protein targeting and serves to activate hedgehog (HH)-mediated signaling. The results of our study suggest that activation of HH-mediated signaling can inhibit adipocyte differentiation. Furthermore, expression of glioma-associated oncogene homologue 1 (Gli1) was detected by flow cytometry in 62.7±1.5% of cells in response to administration of Lactobacillus rhamnosus (KCTC 3237) and in 60.4±2.2% of cells in response to camphor; these levels are higher than those detected in undifferentiated controls (24.9±3.1%). No change in the state of fermented camphor was identified by gas chromatography-mass spectrometry (GC-MS), but a 15.41% quantitative increase was confirmed in KCTC 3237. Overall, we conclude that administration of camphor resulted in overexpression of SMO and modulated the differential expression of Gli1. Animal studies focused on the impact of camphor as an agent to counteract obesity might be considered in the future. Indeed, camphor and similar physiologically active compounds from fermented CI might be developed as new and effective treatments for obesity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4001-4005
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• 2012

Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs $28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.

• Molecules and Cells
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• v.41 no.3
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• pp.224-233
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• 2018

Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.1
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• pp.73-79
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• 2018

The primary cilium protrudes from the cell body like a bio-antenna that has many receptors, channels and signaling molecules to sense and response to external stimuli. The external environment such as ultraviolet irradiation, temperature, humidity, gravity and shear stress always influences skin. Skin responds to external stimuli and differentiates by making melanin, collagen and horny layer. Ciliogenesis participates in developmental processes of skin, such as keratinocyte differentiation and hair formation. And it was reported that skin pigmentation was inhibited when ciliogenesis was induced by sonic hedgehog-smoothened-GLI2 signaling. When skin is exposed to ultraviolet irradiation, alpha-melanocyte stimulating hormones (${\alpha}$-MSH) increase melanin synthesis through activation of the cAMP pathway in melanocytes. We observed that ${\alpha}$-MSH and cAMP production inducers inhibited ciliogenesis of melanocytes. Therefore, we thought that regulation of ciliogenesis is potential candidate target for the development of agents to treat undesirable hyperpigmentation of skin. As a result, we found out that an ethanol extract of Glycyrrhiza glabra (EGG) root and 3,4,5-trimethoxy cinnamate thymol ester (TCTE, Melasolv) significantly inhibit melanin synthesis of normal human melanocyte by inducing primary cilium formation. This study proposed new theory to regulate skin pigmentation and cosmetic components for skin whitening.