• Title/Summary/Keyword: TGF-beta

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Anti-atopic Effect of Zizyphus jujuba var. spinosa Composite oil(ZjJ-C_oil) and Aralia cordata var. continentalis Composite oil(ARC-C_oil) in DNCB-induced Atopic Dermatitis-like Skin Lesions NC/Nga Mice (천연물 유래 산조인 복합오일 (Zizyphus jujuba var. spinosa Composite oil, ZjJ-C_oil) 및 독활 복합오일 (Aralia cordata var. continentalis Composite oil, ARC-C_oil)의 DNCB로 유도된 NC/Nga 생쥐의 아토피에 미치는 효과 연구)

  • Kwak, Jin-young;Choir, Hee-Jeong;Park, Jung-mi;Park, Jung-hwan;Kho, Young-mee;Jang, Tae-soo;Ahn, Teakwon
    • Journal of Sasang Constitutional Medicine
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    • v.29 no.4
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    • pp.347-368
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    • 2017
  • The aim of this study is to investigate the effect of Zizyphus jujuba var. spinosa Composite oil(ZjJ-C_oil) and Aralia cordata var. continentalis Composite oil(ARC-C_oil) to NC/Nga mice induced in Atopic dermatitis-like skin lesions by DNCB. NC/Nga mice which have been induced to Atopic dermatitis-like skin lesions by DNCB are divided into 4 groups, the first is the mice which have been spread with izyphus jujuba var. spinosa Composite oil(ZjJ-C_oil), the second is the mice which have been spread with Aralia cordata var. continentalis Composite oil(ARC-C_oil), the third is which have been spread with dexamethasone (Dexa.) 0.5% on their Atopic lesion, the last is the control group. Then We analyzed skin clinical score, blood sample of each group of measure state of the dorsal skin, the number of immunocytes, and resect the skin lesion to anlayze the state of cells. There are meaningful results of measuring the number of IgE, IL-4, IL-13, $IFN-{\gamma}$, IL-5, the total cells in ALN, dorsal skin, CD4+ Th, CD11b+/Gr-1+ in PBMCs, CD4+ Th, B220+/CD23+ in ALN, $CD4^+$, $CD8^+$ Th in dorsal skin, the level of COX-2, $TNF-{\alpha}$, $TGF-{\beta}1$, IL-4, IL-13 mRNA, the state of the skin lesion and cells in the group with ZjJ-C_oil, ARC-C_oil cream in comprarison with the control group.

Effects of Cryptotympana pustulata on the expression of cytokine genes in human monocytes of THP-1 (선퇴가 인간의 THP-1 단핵구에서 사이토카인 유전자 발현에 미치는 영향)

  • An, Jong-Hyun;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.1
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    • pp.94-110
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    • 2010
  • Objective : This study was performed to evaluate the effect of immune reaction inductive substances such as phorbol-myristate-acetate(PMA), lipopolysaccharide(LPS), dermato-phagoides pteronyssus crude extract(DPE), dinitrochloro-benzene(DNCB) and Cryptotympana pustulata(CP), the Cryptotympana pustulata extracting substance at simultaneously on the translocation of nuclear factor-kappa B(NF-${\kappa}B$) towards to the nucleus and the mRNA expression patterns of various cytokine genes in Human acute monocytic leukemia cell line(THP-1 cells), monocytes of human. Experiment : To analyze cytokine genes expression patterns, the RT-PCR method was used, measuring tumor necrosis factor(TNF)-$\alpha$ that had been secreted during cell culture in the ELISA method. The morphological change in the cell observed during THP-1 cell culture was observed using a scanning electron microscope (SEM) and the quantitative distribution in the cell NF-${\kappa}B$ was analyzed through immunocytochemistry and a confocal microscopy. Result : CP showed different influences onto the mRNA expression patterns of cytokine genes with PMA, LPS. DPE and DNCB according to the types of immune inductive substances in the THP-1 cells. The expressions of inter-leukin(IL)-10, interferon(INF)-$\gamma$, TNF-$\alpha$ and monocyte chemoattractantant protein(MCP)-1 induced by PMA were suppressed by CP while the expression of transforming growth factor(TGF)-$\beta$ was promoted. Regarding the secretion pattern of TNF-$\alpha$ according to PMA processing, its secretion amount was increased by CP concurrent processing, in case of processing CP onto PMA and LPS, We discovered that the secretion amount of TNF-$\alpha$ was increased. Upon processing PMA and LPS on the THP-1 cell strain at the same time or either additionally processing CP thereon, the movement increase towards the nucleus from the NF-${\kappa}B$ cell cytoplasm, a transcription factor was able to be observed. Conclusion : In this study, Cryptotympana pustulata extracting substance was confirmed that it had an influence on expression patterns of cytokine genes according to the actions of a variety kinds of immune reaction inductive substances processed on the monocyte THP-1 cell of humans. Therefore, additional studies as for the immune adjusting function of Cryptotympana pustulata are considered to be able to offer important materials for curing immune abnormal diseases such as atopy dermatitis afterward.

Anti-diabetic and Anti-Inflammatory Effects of Water Extract of Ligustrum japonicum Leaves in db/db Mouse (당뇨병 동물모델에서 여정엽(女貞葉) 추출물의 항당뇨 및 항염증 효과)

  • Lee, Yun Jung;Lee, Yun Jae;Yoon, Jung Joo;Lee, So Min;Kim, Hye Yoom;Shin, Sun Ho;Kang, Dae Gill;Lee, Ho Sub
    • The Korea Journal of Herbology
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    • v.27 no.6
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    • pp.107-114
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    • 2012
  • Objectives : In this study, we investigated the anti-diabetic and anti-inflammatory effects of water extract from leaves of Ligustrum japonicum (WLJ) in db/db mouse. Methods : The db/db mice were treated orally with WLJ (300 mg/kg/day) for 10 weeks to examine the long-term effects on hyperglycemia and glomerular tissue as well as biochemical and functional abnormalities in the kidney. Results : WLJ treatment markedly reduced plasma levels of glucose, triglyceride, creatinine, and systolic blood pressure in diabetic db/db mouse. Treatment of WLJ significantly increased plasma level of high density lipoprotein (HDL)-cholesterol. We also found that overexpressions of vascular cellular adhesion molecule (VCAM)-1 and endothelin (ET)-1 were observed in aortic tissue of db/db mouse, whereas, WLJ suppressed both expression of VCAM-1 and ET-1 in aorta. In renal tissue, overexpressions of ICAM-1 and TGF-${\beta}1$ were found in untreated db/db mouse, however, significantly decreased those levels by WLJ treatment. The insulin immunoreactivity of the pancreatic islets remarkably increased in WLJ treated db/db mouse compared with untreated db/db mouse. Taken together, WLJ treatment ameliorated hyperglycemia and hyperlipidemia via improvement of insulin secretion and lipid metabolism, respectively. Furthermore, WLJ treatment also ameliorated hypertension via inhibition of inflammatory process in vascular and renal tissues. Conclusions : Ligustrum japonicum has an anti-diabetic and anti-inflammatory effects in db/db mouse. Thus, these results suggested a beneficial effect of Ligustrum japonicum in treatment with diabetes and diabetic vasculopathy.

Antioxidant Activity of Cannabidiol (CBD) and Effect on Its Proliferation in Human Dermal Papilla Cells (칸나비디올(CBD)의 항산화 활성 및 인간 모유두 세포 증식에 미치는 영향)

  • Soo Hyun Kim;Kyu-Sang Sim;Jung Yoon Cheon;Jae-Woong Jang;Su Jin Jeong;Ye Hei Seo;Hye Myoung Ahn;Bong-Geun Song;Gi-Seok Kwon;Jung-Bok Lee
    • Journal of Life Science
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    • v.33 no.3
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    • pp.234-241
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    • 2023
  • At present, many countries around the world are legalizing cannabis and its products, and research on various treatments using cannabis is being actively conducted. However, the cannabis plant contains other compounds whose biological effects have not yet been established. We investigated the effect of cannabidiol (CBD) on hair growth in human dermal papilla cells (HDPCs). 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of CBD. The HDPCs viability of CBD was examined via water-soluble tetrazolium salt (WST-1) assay. The expression of hair-loss-related markers in HDPCs by CBD treatment was analyzed by real-time PCR and western blotting. The DPPH, ABTS radical scavenging activity assay showed that CBD had superior antioxidant activities. In HDPCs, CBD increased cellular proliferation at concentrations without cytotoxicity. It also increased the expressions of fibroblast growth factor 1 (FGF1), fibroblast growth factor 7 (FGF7), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF). These results correlated with a decrease in the expression of inhibition-related factors, such as androgen receptor (AR) and transforming growth factor beta 1 (TGF-B1). Moreover, CBD resulted in a significant increase in the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). Therefore, it is suggested that CBD may be a potential remedy for the treatment of alopecia.

The TGFβ→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1

  • Min-Kyu Kim;Sang-Hyun Han;Tae-Geun Park;Soo-Hyun Song;Ja-Youl Lee;You-Soub Lee;Seo-Yeong Yoo;Xin-Zi Chi;Eung-Gook Kim;Ju-Won Jang;Dae Sik Lim;Andre J. van Wijnen;Jung-Won Lee;Suk-Chul Bae
    • Molecules and Cells
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    • v.46 no.10
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    • pp.592-610
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    • 2023
  • The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

The Role of Uteroglobin in the Immunomodulation of Nonsmall Cell Lung Cancer Cells (비소세포 폐암세포에서 Uteroglobin의 면역 조절 기능에 대한 연구)

  • Yoon, Jung Min;Lim, Jae-Jun;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung Koo;Shim, Young-Soo;Kim, Young Whan
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.4
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    • pp.336-344
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    • 2004
  • Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

Anti-Melanogenic, Anti-Wrinkle, Anti-Inflammatory and Anti-Oxidant Effects of Xylosma congesta leaf Ethanol Extract (산유자 잎 에탄올 추출물의 미백, 주름억제, 항염증 및 항산화 효능)

  • Lee, Jae Yeon;Ahn, Eun-Kyung;Ko, Hye-Jin;Cho, Young-Rak;Ko, Woon Chul;Jung, Yong-Hwan;Choi, Kyung-Min;Choi, Mi-Rae;Oh, Joa Sub
    • Journal of Applied Biological Chemistry
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    • v.57 no.4
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    • pp.365-371
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    • 2014
  • In the present study, we investigated the biological activities of Xylosma congesta leaf ethanol extract (XCO) using a variety of in vitro and cell culture model systems for anti-melanogenic, anti-wrinkle, anti-inflammatory and anti-oxidant activities. First, XCO markedly inhibited ${\alpha}$-melanocyte stimulating hormone-stimulated melanin synthesis in B16F10 cells. Secondly, XCO marginally induced procollagen synthesis in CCD-986SK cells. Thirdly, XCO dose-dependently suppressed lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells. XCO did not affect cell viability at different concentrations used in this study, indicating that XCO-mediated inhibition of melanin, procollagen and NO synthesis is not mediated by cytotoxicity. Finally, XCO was found to exert anti-oxidant effect. Taken together, these findings demonstrate for the first time that XCO possesses anti-melanogenic, anti-wrinkle, anti-inflammatory and anti-oxidant activities, and suggest further evaluation and development of XCO as a functional supplement or cosmetic that may be useful for whitening skin, reducing wrinkles and treating inflammatory responses.

Immunohistochemical Studies for TIMP-1 and TIMP-2 Expression after Irradiation in Lung, Liver and Kidney of C57BL/6 Mouse (C57BL/96 Mouse의 폐, 간, 신장에서 방사선조사 후 TIMP-1, TIMP-2의 발현에 대한 면역조직화학적 연구)

  • Noh, Young-Ju;Ahn, Seung-Do;Kim, Jong-Hoon;Choi, Eun-Kyung;Chang, Hye-Sook
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.181-189
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    • 2001
  • Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

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Effects of Black Soybean and Fermented Black Soybean Extracts on Proliferation of Human Follicle Dermal Papilla Cells (검은콩과 발효검은콩 추출물이 인간 모유두 세포 성장에 미치는 효과)

  • Choi, Ji-Hye;Lee, Myoungsook;Kim, Hyun Jung;Kwon, Jung Il;Lee, Yunkyoung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.6
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    • pp.671-680
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    • 2017
  • This study was conducted to examine the effects and potential mechanisms of action of black soybean extracts and fermented black soybean extracts by Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animals subsp. lactis BB-12 (BB-12) on proliferation of human follicle dermal papilla cells (HFDPC). We examined changes in pH, total polyphenol, sugar, and reducing sugar contents according to fermentation period of black soybean extracts. Assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was performed to determine cell toxicity levels of the four black soybean extracts [black soybean water extract (BWE), black soybean ethanol extract (BEE), fermented BWE (F-BEW), and fermented BEE (F-BEE)]. Changes in mRNA expression levels of hair growth promoting factors and hair growth inhibiting factors by the four black soybean extracts were measured by real-time PCR. In addition, phosphorylation levels of mitogen-activated protein kinase family proteins were measured by western blot analysis. As a result, fermentation of black soybeans significantly reduced pH, total polyphenols, and sugar/reducing sugar contents. All four black soybean extracts showed no cellular toxicity in HFDPC. In fact, BEE significantly enhanced cell viability of HFDPC at $100{\mu}g/mL$ compared to control. BWE, BEE, and BWE-F significantly increased mRNA expression of vascular endothelial growth factor, and all four extracts increased mRNA expression of fibroblast growth factor. However, mRNA expression levels of apoptosis-related genes were not affected by black soybean extracts in HFDPC. Furthermore, BWE, BEE, and BWE-F significantly increased phosphorylation levels of extracellular signal-regulated kinase compared to control. Taken together, we demonstrated that black soybean extracts enhanced proliferation of human follicle dermal papilla cells partially via activation of hair growth promoting factors, although no particular significant effects on proliferation were observed by fermentation of black soybeans.

The Relation between Obesity and Glomerular Filtration Rate in Children and Adolescents (소아 및 청소년에서 비만과 사구체여과율과의 관계)

  • Jung, Youngsu;Kim, Dongwoon;Lim, Inseok
    • Clinical and Experimental Pediatrics
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    • v.48 no.11
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    • pp.1219-1224
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    • 2005
  • Purpose : The prevalence of obesity in children and adolescents has been rising rapidly in Korea because of changes of diet and lifestyle. As with adults, obesity in children and adolescents can cause diabetes mellitus, hyperlipidemia, cardiovascular diseases and renal diseases. The aim of the present study is to examine the relation of obesity, glomerular filtration rate(GFR) and serum cystatin C concentration in children and adolescents. Methods : Data of 115 children and adolescents aged between 6 years and 20 years without clinical evidence of renal diseases were included in the study. From May 2004 to December 2004, blood samples were collected from children and adolescents who were seen at the Department of Pediatrics at Chungang University Yongsan Hospital. Obesity degrees and body mass indices(BMI) were measured, and GFRs were estimated from Schwartz's formula. Serum cystatin C was measured by particle enhanced nephelometric immunoassay using Behring Nephelometer II. Results : GFRs were significantly different between the obese group(BMI >95 percentile, $145.79{\pm}23.10mL/min$) and the non-obese group(BMI <95 percentile, $134.61{\pm}26.19mL/min$) divided by BMI (P=0.031). GFRs were not significantly different between the obese group(obesity degree >120 percent, $144.29{\pm}23.08mL/min$) and the non-obese group(obesity degree <120 percent, $134.54{\pm}26.57mL/min$) divided by obesity degree(P=0.051), but were significantly different between severe obese group (obesity degree >150 percent, $155.55{\pm}20.40mL/min$) and the non-obese group(P=0.004). GFRs were correlated positively with BMI($r^2=0.037$, P=0.039), but were not correlated significantly with obesity degree($r^2=0.030$, P=0.066). Serum cystatin C concentrations were not significantly different between the obese group and the non-obese group, divided by BMI as well as by obesity degree(P>0.05). Conclusion : Obesity may lead to an alteration of renal hemodynamics such as hyperfiltration, appropriate control and management for obesity is necessary.