• BMB Reports
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• v.56 no.7
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• pp.374-384
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• 2023

Fibrosis is a pathological condition that is characterized by an abnormal buildup of extracellular matrix (ECM) components, such as collagen, in tissues. This condition affects various organs of the body, including the liver and kidney. Early diagnosis and treatment of fibrosis are crucial, as it is a progressive and irreversible process in both organs. While there are certain similarities in the fibrosis process between the liver and kidney, there are also significant differences that must be identified to determine molecular diagnostic markers and potential therapeutic targets. Long non-coding RNAs (lncRNAs), a class of RNA molecules that do not code for proteins, are increasingly recognized as playing significant roles in gene expression regulation. Emerging evidence suggests that specific lncRNAs are involved in fibrosis development and progression by modulating signaling pathways, such as the TGF-β/Smad pathway and the β-catenin pathway. Thus, identifying the precise lncRNAs involved in fibrosis could lead to novel therapeutic approaches for fibrotic diseases. In this review, we summarize lncRNAs related to fibrosis in the liver and kidney, and propose their potential as therapeutic targets based on their functions.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.3
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• pp.74-94
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• 2016

Objectives : YangHyulEum Gami-Bang(YHEG) is a hair care extracts which is composed of fourteen plant extracts used in oriental medicine. The purpose of this study is to investigate the effect of YangHyulEum Gami-Bang(YHEG) on the alopecia and hair growth.Methods & Results : The herbal extracts from YangHyulEum Gami-Bang(YHEG) was tested using in vivo and in vitro test models. 1. The YHEG extracts showed effect on the DNA proliferation of the hair dermal papilla cells measured by [3H]thymidine incorporation. 2. YHEG showed promoting on the expression of growth factors such as IGF-1, KGF-1 and inhibiting on the expression of inhibitory hair growth factor such as TGF-β1, BMP-2 estimated by qPCR. 3. The YHEG extracts showed effect on the activation of β-catenin in the dermal papilla cells. 4. YHEG showed inhibitory effects of NO synthesis at 0.2% concentrations. 5. YHEG showed effects in the expression of IL-1β, TNF-α, IL-6, COX-2 and iNOS gene in the LPS stimulated RAW 264.7 cells. 6. The hair growth index of the YHEG extracts ranked at over 2 when compared to control group which was ranked at 0. 7. The hair follicle number, length and size of the experimental group were remarkably higher than the control group in the histological observation.Conclusions : These results suggest that YangHyulEum Gami-Bang(YHEG) has hair growth promoting activity and it can be used as a potent treatment agent for preventing hair loss and stimulating hair growth for treatment of alopecia.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.2
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• pp.19-35
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• 2020

Objectives The aim of this study is to evaluate the fracture healing effect of Jinmu-tang (JM) on femur fractured rats. Methods Rats were randomly divided into 5 groups (normal, control, positive control, JM extract with low concentration and JM extract with high concentration). All group except normal group went through both femur fracture. Normal and control group received no treatment at all. Positive control group were medicated with tramadol (20 mg/kg) once a day for 14 days. Experimental group was orally medicated with JM extract (10 mg/kg for low concentration, 50 mg/kg for high concentration) once a day for 14 days. In order to investigate fracture healing process, plasma and serum were obtained. Also, micro-computed tomography was conducted to see the frature site visually. Immunohistochemistry for transforming growth factor-β1, Ki67, alkaline phosphatase, runt-related transcription factor 2, receptor activator of nuclear factor kappa-β, tartrate resistant acid phosphatase was conducted to observe bone healing progress after 14 days since fracture occured. Aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine levels were measured in plasma, for hepatotoxicity and nephrotoxicity of JM extract. Osteocalcin was measured to observe activity of osteoblast. Results Through Micro-CT, more fracture healing was observed on both experimental group than control and positive control group. Through Hematoxylin & Eosin and safranin O staining showed bone cell proliferation and bone formation in the experimental group. RANK was significantly increased in the experimental groups. JM with high concentration showed statistically significant of TGF-β and Osteocalcin. NO, TRAP and ALP were not significantly changed. Liver toxicity was not significantly observed. Creatinine significantly increased in both experimental groups after 28 days. Conclusions As described above, JM extract showed anti-inflammatory effect, promoted fracture healing by stimulating the bone regeneration factor, and showed little hepatotoxicity and nephrotoxicity. In conclusion, JM extract can promote fracture healing and it can be used clinically to patients with fracture.

• BMB Reports
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• v.38 no.1
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• pp.1-8
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• 2005

Transforming growth factor-$\beta$ is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-$\beta$ signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-$\beta$. To name a few, dysregulation of transforming growth factor-$\beta$ signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-$\beta$.

• BMB Reports
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• v.56 no.2
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• pp.65-70
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• 2023

Prominin-1 (PROM1), also called CD133, is a penta-span transmembrane protein that is localized in membrane protrusions, such as microvilli and filopodia. It is known to be expressed in cancer stem cells and various progenitor cells of bone marrow, liver, kidney, and intestine. Accumulating evidence has revealed that PROM1 has multiple functions in various organs, such as eye, tooth, peripheral nerve, and liver, associating with various molecular protein partners. PROM1 regulates PKA-induced gluconeogenesis, TGFβ-induced fibrosis, and IL-6-induced regeneration in the liver, associating with Radixin, SMAD7, and GP130, respectively. In addition, PROM1 is necessary to maintain cancer stem cell properties by activating PI3K and β-Catenin. PROM1-deficienct mice also show distinct phenotypes in eyes, brain, peripheral nerves, and tooth. Here, we discuss recent findings of PROM1-mediated signal transduction.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.259-259
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• 2021

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.289-294
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• 2012

Background: Myofibroblasts play an important role in the development of oral submucous fibrosis (OSF). In the current study, we investigate the effect of curcumin on growth and apoptosis of myofibroblasts derived from human oral mucosa. Methods: Myofibroblasts were generated by incubating fibroblasts, obtained from human oral mucosa, with transforming growth factor-${\beta}1$ (TGF-${\beta}1$). MTT, PI staining, and FACS assays were used to investigate curcumin's effect on proliferation and cell cycle of fibroblasts and myofibroblasts. Annexin V/PI binding and FACS assays were used to examine apoptosis of myofibroblasts, Western blotting to determine the levels of Bcl-2 and Bax, and enzyme-linked immunosorbant assay was employed to examine the levels of collagen type I and III in the supernatants of myofibroblasts. Results: Curcumin inhibits proliferation of fibroblasts and myofibroblasts; it also disturbs the cell cycle, induces apoptosis and decreases the generation of collagen type I and III in myofibroblasts, which are more sensitive to its effects than fibroblasts. Curcumin induces apoptosis in myofibroblasts by down-regulating the Bcl-2/ Bax ratio. Conclusion: Our results demonstrate the antifibrotic effect of curcumin in vitro. It may therefore be a candidate for the treatment of OSF.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.315-320
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• 2013

Background: TGF-${\beta}$-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. Methods: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. Results: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. Conclusions: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.

• Laboraroty Animal Research
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• v.33 no.2
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• pp.76-83
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• 2017

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.781-791
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• 2018

BACKGROUND: Glucosamine hydrochloride (GlcN HCl) has been shown to inhibit cell growth and matrix synthesis, but not with N-acetyl-glucosamine (GlcNAc) supplementation. This effect might be related to an inhibition of critical growth factors (GF), or to a different metabolization of the two glucosamine derivatives. The aim of the present study was to evaluate the synergy between GlcN HCl, GlcNAc, and GF on proliferation and cartilage matrix synthesis. METHOD: Bovine chondrocytes were cultivated in monolayers for 48 h and in three-dimensional (3D) chitosan scaffolds for 30 days in perfusion bioreactors. Serum-free (SF) medium was supplemented with either growth factors (GF) $TGF-{\beta}$ ($5ng\;mL^{-1}$) and IGF-I ($10ng\;mL^{-1}$), GlcN HCl or GlcNAc at 1mM each or both. Six groups were compared according to medium supplementation: (a) SF control; (b) SF + GlcN HCl; (c) SF + GlcNAc; (d) SF + GF; (e) SF + GF + GlcN HCl; and (f) SF + GF + GlcNAc. Cell proliferation, proteoglycan, collagen I (COL1), and collagen II (COL2) synthesis were evaluated. RESULTS: The two glucosamines showed opposite effects in monolayer culture: GlcN HCl significantly reduced proliferation and GlcNAc significantly augmented cellular metabolism. In the 30 days 3D culture, the GlcN HCl added to GF stimulated cell proliferation more than when compared to GF only, but the proteoglycan synthesis was smaller than GF. However, GlcNAc added to GF improved the cell proliferation and proteoglycan synthesis more than when compared to GF and GF/GlcN HCl. The synthesis of COL1 and COL2 was observed in all groups containing GF. CONCLUSION: GlcN HCl and GlcNAc increased cell growth and stimulated COL2 synthesis in long-time 3D culture. However, only GlcNAc added to GF improved proteoglycan synthesis.