Resistin upregulates <i>MUC5AC/B</i> mucin gene expression in human airway epithelial cells

Kwak, Soyoung,Kim, Yong-Dae,Na, Hyung Gyun,Bae, Chang Hoon,Song, Si-Youn,Choi, Yoon Seok Elsevier 2018 Biochemical and biophysical research communication Vol.499 No.3

<P><B>Abstract</B></P> <P>Adipokines, a group of proteins including leptin, visfatin, resistin, and adiponectin, are produced by adipocytes. Among adipokines, resistin is implicated in insulin resistance and inflammatory response modulation. Mucus hypersecretion has been greatly linked to airway diseases, such as asthma, chronic obstructive pulmonary disease, and rhinosinusitis. Increasing evidence has indicated that adipokines, such as leptin and visfatin, play important regulatory roles in various biological processes involved in mucus secretion. However, the effects of resistin on mucin expression in human airway epithelial cells, as well as the underlying mechanisms, have not been investigated yet. We showed that resistin affected mucin expression in human airway epithelial cells <I>via</I> the mitogen-activated protein kinase/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Resistin increased MUC5AC and MUC5B expression in NCI-H292 and primary human nasal epithelial cells. Additionally, it significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and NF-κB. ERK1/2 and p38 specific inhibitors significantly attenuated resistin-induced MUC5AC/5B expression; however, NF-κB inhibitor reduced resistin-induced MUC5AC, but not MUC5B, expression. Knockdown of ERK1, ERK2, and p38 by ERK1, ERK2, and p38 small interfering RNA (siRNA), respectively, significantly blocked resistin-induced MUC5AC and MUC5B mRNA expression. In addition, NF-κB siRNA attenuated resistin-induced MUC5AC, but not MUC5B, expression. These results suggested that resistin induced MUC5AC and MUC5B expression <I>via</I> activation of different signaling pathways in human airway epithelial cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Resistin are implicated in modulation of airway mucin secretion. </LI> <LI> Resistin induce MUC5AC and MUC5B expression. </LI> <LI> Resistin induce MUC5AC expression via ERK1/2, p38 MAPK, and NF-kB. </LI> <LI> Resistin induce MUC5B expression via ERK1/2 and p38 MAPK. </LI> </UL> </P>

Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis

Elsayed, Engy Yousry,Mosalam, Nesreen Ahmed,Mohamed, Noha Refaat Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. Materials and Methods: This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. Results: HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA > 4 being 1.6 times more likely to have HCC. Conclusions: HOMA and serum resistin allow for early identification of patients with cirrhosiswho are at substantially increased risk of HCC. Recommendation: HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.

Caffeic Acid DisturbsMonocyte Adhesion onto CulturedEndothelial Cells Stimulated by Adipokine Resistin

Lee, Eun-Sook,Park, Sin-Hye,Kim, Min Soo,Han, Seon-Young,Kim, Hyun-Sung,Kang, Young-Hee American Chemical Society 2012 Journal of agricultural and food chemistry Vol.60 No.10

<P>Adipokines have been implicated in the pathogenesis of atherosclerosis via pro-inflammatory mechanisms contributing to insulin resistance. The adipokine resistin causes endothelium dysfunction, which plays an important role in sustaining atherogenesis. This study investigated whether resistin induced expression of cell adhesion molecules and integrins in endothelial cells and THP-1 monocytes and whether such induction was attenuated by 1-20 mu M caffeic acid. Resistin enhanced endothelial expression of vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1), and E-selectin and monocyte expression of beta 1, beta 2, and alpha 4 integrins. The enhancement of these proteins was diminished by caffeic acid with reduced THP-1 cell adhesion on activated endothelium. Caffeic acid at <= 20 mu M demoted resistin-stimulated interleukin 8 (IL-8) production responsible for ICAM-1 and beta 2 integrin induction. The endothelial up-regulation of IL-8 secretion by resistin entailed toll-like receptor 4 (TLR4) activation, but caffeic acid diminished IL-8 production and TLR4 induction. Furthermore, caffeic acid encumbered resistin-activated nuclear factor kappa B (NF-kappa B) signaling. These results demonstrate that caffeic acid blocked monocyte trafficking to resistin-activated endothelium via disturbing NF-kappa B signaling responsive to IL-8. Therefore, caffeic acid may have therapeutic potential in preventing obesity-associated atherosclerosis.</P>

Resistin derived from diabetic perivascular adipose tissue up-regulates vascular expression of osteopontin via the AP-1 signalling pathway

Park, So Youn,Kim, Kyu Hee,Seo, Kyo Won,Bae, Jin Ung,Kim, Yun Hak,Lee, Seung Jin,Lee, Won Suk,Kim, Chi Dae John WileySons, Ltd 2014 The Journal of pathology Vol.232 No.1

<P>Perivascular adipose tissue (PVAT) is implicated in the development of vascular diseases; however, the roles of PVAT on OPN expression in diabetic vasculature remain to be determined. This study investigated the role of adipokines derived from diabetic PVAT in regulating the vascular expression of OPN and explored the mechanisms involved. Aortic sections of ob/ob and high-fat diet (HFD)-induced obese (DIO) mice showed an increased expression of OPN, which was paralleled by increased amounts of PVAT characterized by enlargement of adipocytes. In the earlier phase of HFD feeding, macrophage infiltration was mainly localized to the area of PVAT at which adipocytes were enlarged, suggesting a potential link of activated adipocytes to macrophage infiltration. PVAT sections of ob/ob and DIO mice revealed a significantly greater number of macrophages with increased expression of adipokines, including resistin and visfatin. The distribution of resistin in PVAT mostly co-localized with macrophages, while visfatin was expressed in macrophages and other cells. In <I>in vitro</I> studies, OPN expression in vascular smooth muscle cells (VSMCs) co-cultured with PVAT of DIO mice was significantly increased, which was attenuated by a resistin-neutralizing antibody. Likewise, resistin up-regulated expression of <I>OPN</I> mRNA and protein in cultured VSMCs and the pivotal role of AP-1 in resistin-induced OPN transcription was demonstrated. Resistin produced by PVAT plays a pivotal role in the up-regulated expression of OPN in the diabetic vasculature via a signalling pathway that involves activation of AP-1. © 2013 The Authors. <I>Journal of Pathology</I> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</P>

필라테스 매트 운동이 비만 중년여성의 건강관련체력과 Adiponectin, Resistin에 미치는 영향

김남정(Kim, Nam-Jung) 한국체육과학회 2013 한국체육과학회지 Vol.22 No.5

The purpose of this study was to determine the effects of pilates mat exercise on health related physical fitness and adiponectin, resistin in the middle-aged obese women. The subjects of this research were twenty middle-aged obese women(over 30% of body fat percentage) without any metabolic diseases and haven"t had regular and vigorous physical activities for the last six months. In order to determine the effects of pilates mat exercise on health related physical fitness and plasma level of adiponectin and resistin, subjects were randomly divided into two groups; Exercise group(n=10) and Control group(n=10). The subjects of exercise group were required to performed pilates mat exercise 3 times a week for 90 minutes for 10 weeks. All subjects of this study were examined the changes in health related physical fitness(weight, body fat, musclar strength, muscular endurance, flexibility, cardiorespiratory endurance) and plasma level of adiponectin and resistin. The results of the study in the exercise group were as follows; The weight, body fat, resistin had significantly decreased and adiponectin, musclar strength, muscular endurance, flexibility had significantly increased. And also, regular pilates mat exercise can positive effective to improving health related physical fitness and adiponectin, resistin.

비만 아동에서 leptin, adiponectin 및 resistin의 혈중농도와 인슐린 저항성과의 관계

박민영,안선아,조원경,조경순,박소현,한승훈,정민호,서병규 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.7

Purpose : The objective of this study was to compare the levels of adipocytokines in obesity group with those in control group and examine their correlation with insulin resistance. Methods : We enrolled 36 obese children (male:female [M:F]=17:19; age, 9.3±1.9 yrs) with ≥95th percentile body mass indexes (BMIs) (obesity group) and 35 healthy children (M:F=16:19; age, 9.1±2.1 yrs) with 25th-75th percentile BMIs (control group). We measured the serum leptin, adiponectin, and resistin levels and insulin resistance in both the groups. Results : The weights, heights, BMIs, fasting sugar levels, insulin levels, and homeostasis model assessment for insulin resistance (HOMA-IR) values were higher in the obesity group than in the control group. As compared to the control group, the obesity group showed significantly higher leptin levels and lower adiponectin levels; no significant difference was observed in the resistin levels. The leptin/adiponectin (L/A) ratio was higher in the obesity group than in the control group. In the obesity group, HOMA-IR showed significant positive correlations with weight, height, BMI, and leptin level. However, it was not correlated with age and adiponectin and resistin levels. In the obesity group, leptin level showed significant positive correlations with age, weight, height, and BMI, while adiponectin and resistin levels showed no such correlations with the other variables. Conclusion : We suggest that adiponectin plays an important protective role against weight gain in obese children. Further, L/A ratio can be used as a parameter for predicting the prognosis of obese children. 목 적 : 대사증후군은 심혈관계질환과 고지혈증, 비만, 당뇨병 등의 증상을 나타내는 증후군으로 최근 소아청소년 연령에서 유병률이 증가하고 있다. 대사증후군을 일으키는 주된 병태생리는 인슐린 저항성이다. 최근에 와서 체내의 지방조직은 혈중에 여러 아디포사이토카인들을 분비하여 인슐린 감수성을 조절한다고 알려졌다. 저자들은 비만 아동의 혈중 렙틴, 아디포넥틴 및 레지스틴등의 혈중 농도를 측정하여 정상 아동과 비교하였으며 이들 사이토카인들과 인슐린 저항성과의 상관관계도 알아보고자 하였다. 방 법 : 비만아 36명(남 17명, 여 19명)의 평균연령은 9.3±1.9 세였고 평균 체질량지수(BMI)는 23.2±2.6 kg/㎡ 였다. 정상대조군 35명(남 16명, 여 19명)의 평균연령은 9.1±2.1세였으며 평균 체질량 지수는 16.8±1.4 kg/㎡ 였다. 결 과 : 비만군에서 정상대조군보다 체중, 신장 및 BMI가 유의하게 차이가 있었으며 공복혈당, 인슐린 농도가 높았으며 인슐린 저항성의 지표인 HOMA-IR도 유의하게 높았다. 또 비만군에서 혈중 렙틴농도가 유의하게 높았고(P<0.001) 아디포텍틴은 유의하게 낮았다(P<0.001). 혈중 레지스틴은 두 군간에 차이가 없었다. 렙틴/아디포넥틴 비는 비만군에서 유의하게 높았다(P< 0.001). 또 비만군에서 HOMA-IR은 체중, 신장, BMI및 렙틴과 양의 상관관계가 있었으나 연령, 아디포넥틴, 레지스틴과는 상관이 없었다. 비만군에서 렙틴은 연령, 체중, 신장 및 BMI와 양의 상관관계가 있었으나 아디포넥틴 과 레지스틴은 기타변수와 상관이 없었다. 결 론 : 비만군에서 렙틴/아디포넥틴 비는 인슐린 저항성과 의미있는 연관성이 있어 향후 비만의 예후를 추정하는 변수로 이용될 수 있을 것으로 생각되며 비만군에서 아디포넥틴이 감소되어 있었다는 것은 아디포넥틴이 비만 발생의 억제기전에 중요한 역할을 할 것으로 생각된다.

경도정신지체 비만청소년에게 무용프로그램 적용이 비만지표와 혈중 렙틴, 레지스틴 및 아디포넥틴에 미치는 영향

권혜영(Kwon Hye-Young),이원재(Lee Won-Jae),주성범(Ju Sung-Bum) 한국체육과학회 2009 한국체육과학회지 Vol.18 No.3

The purpose of the study was to identify the effects of dance program on obesity indices, blood leptin, resistin and adiponectin of obese adolescence of mental retardation. For the purpose of this study, we selected 16 mentally retareded obese adolescence and divided them into two groups; 8 obese adolescence of mental retardation for dance program group and 8 control group. We asked them to dance program for 12 weeks and then analyzed the effects of the program on the obesity indices/body composition, blood lipid concentration) and blood leptin, resistin and adiponectin. Regarding the changes in obesity indices, dance program group showed significant reduction in fat mass, %body fat 9"oabdominal fat and significant reduction in LDL-C after application of the dance program. Regarding the changes in blood leptin, resistin and adiponectin, adiponectin increased significantly and resistin decreased significantly after application of the dance program To conclude, Applying of dance program for obese adolescence of mental retardation will be effectively appeared to decreasing of obesity indices and positive effects blood adiponectin, resistin.

걷기운동과 복합운동의 비만 청소년의 신체조성과 심혈관계 질환 관련 Cytokine에 미치는 영향

황은아 ( Eun A Hwang ),김선희 ( Sun Hee Kim ),강희성 ( Hi Sung Kang ),김종식 ( Jong Shik Kim ) 한국운동생리학회(구-한국운동과학회) 2012 운동과학 Vol.21 No.1

본 연구에서는 12주간의 걷기운동과 복합운동 프로그램이 비만 청소년의 성혈관계 질환과 관련이 있는 Cytokine IL-6, CRP, Resistin에 미치는 효과를 규명하고자 하였다. 걷기운동은 주 4-5회. 1-5주까지는 45-60%HPmax, 6-12주까지는 61-70%HPmax의 운동강도로 주기별 점증적으로 증가시켰으며, 저항운동으로는 웨이트 트레이닝을 최대근력(lRM)의 60-70%로 반복횟수 10-12회, 3세트로 20분간 실시하였다. 걷기운동집단과 복합운동집단 모두 체중, 체지방률, BMI에서 유의한 변화를 나타내고 있으나 감소폭은 복합운동집단이 더욱 큰 것으로 나타났다. IL-6 농도의 변화에서는 복합운동집단은 유의하게 감소하였으나(p<.0.5), 걷기운동집단은 통계적으로 유의차는 나타나지 않았지만 감소가 나타났다. CRP 농도의 변화에서는 걷기운동집단운 유의하게 감소하였고(p<.05), 복합운동집단은 걷기운동집단보다 더욱 큰 차이를 나타내며 유의하게 감소하였다(p<.01). Resistin 농도의 변화헤서는 복합운동집단의 경우 유의하게 감소하였다(p<.05) 하지만 걷기운동집단의 경우는 특별한 변화가 나타나지 않았다. 이상에서 살펴본 바와 같이, 복합운동 프로그램이 심혈관 질환 관련 Cytokine IL-6, CRP, Resistin에서 긍정적인 변화를 가져왔으며, 이는 규칙적인 복합운동이 비만 청소년들의 심혈관계 질환 및 대사성 질환의 위험도를 긍정적으로 개선시킨 것으로 생각된다. The purpose of this study was to investigate the effects of twelve weeks combined exercise on IL-6, CRP, Resistin related to cardiovascular disease in obese adolescents. The walking exercise group performed walking program on a treadmill, 4-5 times a week (1-5 weeks; at the intensity of 45-60% HRmax, 6-12 weeks; at the intensity of 61-70% HRmax), the resistance exercise group performed weight training in 20min (intensity; lRM. 60-70%, repetition; 10-12 per a set, 3 sets). There was a significant, positive change in the body compositions such as body weight, body fat mass and body mass index (BMI) in both the combined exercise group and the walking exercise group. but the drop rate of the combined exercise group was larger. The changes of IL-6 in the combined exercise group were decreased after 12 weeks of exercise (p<.05), the walking exercise group was decreased but this group has no significant difference in statistical. The changes of CRP in the walking exercise group were significantly decreased after twelve weeks of exercise (p<.05), the combined exercise group was significantly decreased and the drop rate of the changes of CRP is larger than those of the walking exercise group (p<.01). The changes of Resistin in the combined exercise group were significantly decreased (p<.05), but there was no special change in the walking exercise group. Consequently, the combined exercise program had a positive effect on IL-6, CRP, Resistin related to cardiovascular disease, that is to say, the regular combined exercise improves the risk of cardiovascular disease and metabolic syndrome, so that it Will make a great benefit on health for a lifetime.

Generation of Embryonic Stem Cell-derived Transgenic Mice by Using Tetraploid Complementation

Park, S.M.,Song, S.J.,Uhm, S.J.,Cho, S.G.,Park, S.P.,Lim, J.H.,Lee, H.T. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.12

The objective of this study was to generate transgenic mice expressing human resistin gene by using the tetraploidembryonic stem (ES) cell complementation method. Human resistin gene was amplified from human fetal liver cDNA library by PCR, cloned into $pCR^{(R)}$ 2.1 $TOPO^{(R)}$ vector and constructed in pCMV-Tag4C vector. Mammalian expression plasmid containing human resistin was transfected into D3-GL ES cells by Lipofectamine 2,000, and then after 10-12 days of transfection, the human resistin-expressing cells were selected with G418. In order to produce tetraploid embryos, blastomeres of diploid embryos at the two-cell stage were fused with two times of electric pulse using 60 V 30 $\mu$sec (fusion rate: 2,114/2,256, 93.5%) and cultured up to the blastocyst stage (development rate: 1,862/2,114, 94.6%). The selected 15-20 ES cells were injected into tetraploid blastocysts, and then transferred into the uteri of E 2.5 d pseudopregnant recipient mice. To investigate the gestation progress, two E 19.5 mused fetuses were recovered by Cesarean section of which one fetus was confirmed to contain human resistin gene by genomic DNA-PCR. Therefore, our findings demonstrate that tetraploid-ES mouse technology can be considered as a useful tool to produce transgenic mice for the rapid analysis of gene function in vivo.

Generation of Embryonic Stem Cell-derived Transgenic Mice by using Tetraploid Complementation

Park Sun-Mi,Song Sang-Jin,Choi Ho-Jun,Uhm Sang-Jun,Cho Ssang-Goo,Lee Hoon-Taek 한국발생생물학회 2003 한국발생생물학회 학술발표대회 Vol.2003 No.1

The standard protocol for the production of transgenic mouse from ES-injected embryo has to process via chimera producing and several times breeding steps, In contrast, tetraploid-ES cell complementation method allows the immediate generation of targeted murine mutants from genetically modified ES cell clones. The advantage of this advanced technique is a simple and efficient without chimeric intermediates. Recently, this method has been significantly improved through the discovery that ES cells derived from hybrid strains support the development of viable ES mice more efficiently than inbred ES cells do. Therefore, the objective of this study was to generate transgenic mice overexpressing human resistin gene by using tetrapioid-ES cell complementation method. Human resistin gene was amplified from human fetal liver cDNA library by PCR and cloned into pCR 2.1 TOPO T-vector and constructed in pCMV-Tag4C vector. Human resistin mammalian expression plasmid was transfected into D3-GL ES cells by lipofectamine 2000, and then after 8~10 days of transfection, the human resistin-expressing cells were selected with G418. In order to produce tetraploid embryos, blastomeres of diploid embryos at the two-cell stage were fused with two times of electric pulse using 60 V 30 sec. (fusion rate : 93.5%) and cultured upto the blastocyst stage (development rate : 94.6%). The 15~20 previously G418-selected ES cells were injected into tetraploid blastocysts, and then transferred into the uterus of E2.5d pseudopregnant recipient mice. To investigate the gestation progress, two El9.5d fetus were recovered by Casarean section and one fetus was confirmed to contain human resistin gene by genomic DNA-PCR. Therefore, this finding demonstrates that tetraploid-ES mouse technology can be considered as a useful tool to produce transgenic mouse for the rapid analysis of gene function in vivo.