• Title/Summary/Keyword: 억제인자

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Histone H3K4 Methyltransferase SET1A Stimulates the Adipogenesis of 3T3-L1 Preadipocytes (히스톤 H3K4 메칠화효소 SET1A에 의한 지방세포 분화 촉진)

  • Kim, Seon Hoo;Jung, Myeong Ho
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1104-1110
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    • 2017
  • SET1A is a histone H3K4 methyltransferase that catalyzes di- and trimethylation of histone H3 at lysine 4 (H3K4). Mono-, di-, and trimethylations on H3K4 (H3K4me1, H3K4me2, and H3K4me3, respectively) are generally correlated with gene activation. Although H3K4 methylation is associated with the stimulation of adipogenesis of 3T3-L1 preadipocytes, it remains unknown whether SET1A plays a role in the regulation of adipogenesis of 3T3-L1 preadipocytes. Here, we investigated whether SET1A regulates 3T3-L1 preadipocytes' adipogenesis and characterized the mechanism involved in this regulation. SET1A expression increased during 3T3-L1 preadipocytes' adipogenesis. Consistent with the increased SET1A expression, the global H3K4me3 level had also increased on day 2 after the induction of adipogenesis in 3T3-L1 adipocytes. SET1A knockdown using siRNA in 3T3-L1 preadipocytes inhibited 3T3-L1 preadipocytes' adipogenesis, as assessed by Oil Red O staining and the expression of adipogenic genes, indicating that SET1A stimulates the adipogenesis of 3T3-L1 preadipocytes. SET1A knockdown inhibited the cell proliferation of 3T3-L1 cells during mitotic clonal expansion (MCE) via down-regulation of the cell cycle gene cyclin E1, as well as the DNA synthesis gene, dihydrofolate reductase. Furthermore, SET1A knockdown repressed peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) expression during the late stage of adipogenesis. These results indicate that SET1A stimulates MCE and $PPAR{\gamma}$ expression, which leads to the promotion of 3T3-L1 preadipocytes' adipogenesis.

Effects of Treadmill Exercise on Alpha-synuclein Mutation and Activated Neurotrophins in Nigrostriatal Region of MPTP-induced Parkinson Models (MPTP 파킨슨 모델의 트레드밀 운동이 알파시누크린 변성과 흑질선조체내 신경성장인자 활성화에 미치는 영향)

  • Park, Jae-Sung;Kim, Jeong-Hwan;Yoon, Sung-Jin
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.2
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    • pp.73-88
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    • 2009
  • Objectives : Neuronal changes that result from treadmill exercise for patients with Parkinson's disease(PD) have not been well documented, although some clinical and laboratory reports suggest that regular exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. However, it is not clear if the improvements are due to neuronal alterations within the affected nigrostriatal region or result from a more general effect of exercise on affect areas and motivation. In this study, we demonstrate that motorized treadmill exercise improves the neuronal outcomes in rodent models of PD. Methods : We used a chronic mouse model of parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses(Every 12 hour) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) and probenecid (20 mg/kg) over 5 days. These mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, $0^{\circ}$ of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we extracted the brain and compared their neuronal and neurochemical changes with the control(saline and sedentary) mice groups. Synphilin protein is the substance that manifestly reacts with ${\alpha}$-synuclein. In this study, we used Synphilin as a manifest sign of recovery from neurodegeneration. We analyze the brain stems of the substantia nigra and striatum region using the western blotting technique. Results : There were no expression of synphilin in the saline-induced groups. The addition of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) greatly accelerated synphilin expression which meant an aggregation of ${\alpha}$-synuclein. But, the MPTP-induced treadmill exercise group showed significantly lower expression than the MPTP-induced sedentary group. This means treadmill exercise has a definite effect on the decrease of ${\alpha}$-synuclein aggregation. Conclusions : In this study, our results suggest that treadmill exercise promoted the removal of the aggregation of ${\alpha}$-synuclein, resulting in protection against disease development and blocks the apoptotic process in the chronic parkinsonian mice brain with severe neurodegeneration.

The Role of Neutrophils and Epidermal Growth Factor Receptors in Lipopolysaccharide-Induced Mucus Hypersecretion (리포다당질 (lipopolysaccharide)에 의한 기관지 점액 생성 기전에서 호중구와 상피세포 성장인자 수용체 (epidermal growth factor receptor)의 역할)

  • Bak, Sang Myeon;Park, Soo Yeon;Hur, Gyu Young;Lee, Seung Heon;Kim, Je Hyeong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.1
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    • pp.80-90
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    • 2003
  • Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

Effect of Feeding Prunus mume By-products on Productivity and Blood Composition in Semi-Broiler Chicks (매실 부산물 급여가 준육용계의 생산 능력과 혈액 성상에 미치는 영향)

  • Jeong, Y.D.;Cho, I.K.
    • Korean Journal of Poultry Science
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    • v.34 no.4
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    • pp.237-243
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    • 2007
  • The objective of this experiment was to investigate the feeding influence of Prunus memu by-products (PMB) on productivity, blood composition, meat quality and intestinal microflora in semi-broiler chicks. Four hundred one day old chicks(Hanhyup 3) were raised in the floor pen with five treatments(0, 0.5, 1.0 2.0 3.0%) of four replicate for ten weeks. Basal diets contained 3,000, 3,100, 3,100, 3,200 kcal/kg ME and 22, 21, 19, 17% CP, respectively. There were no different performance for the first two weeks, but showed significantly different weight gain, feed intake in PMB 2.0, 3.0% addition treatments compared with control from three to five weeks of age. Weight gain of birds fed 2.0% PMB was significantly higher from nine to 10 weeks of age than control(P<0.05). Total weight gain tended to increase in PMB 1.0, 2.0, 3.0% addition treatments. Feed intake also showed increase in PMB 2.0, 3.0% addition treatments, but there were no different feed conversion. Total protein, albumin, cholesterol, neutral fat, glucose was significantly decreased in PMB 0.5% addition treatments compared with control. There were no different physico-chemical characteristics in breast meat. The number of yeast was significantly improved in PMB 3.0% compared with control(P<0.05), but found no difference in number of E. coli between control and PMB treatments. ND titer of birds fed PMB was not statistically different, but tended to decrease as dietary PMB increased. As the result of this experiment, PMB would be available as a feed additives in semi-broiler chicks.

EXPRESSION AND FUNCTION OF OD314, APIN PROTEIN, DURING AMELOBLAST DIFFERENTIATION AND AMELOGENESIS (법랑모세포 분화와 법랑질 형성과정에서 OD314, Apin protein의 발현 및 기능)

  • Park, Jong-Tae;Choi, Yong-Seok;Kim, Heung-Joong;Jeong, Moon-Jin;Oh, Hyun-Ju;Shin, In-Cheol;Park, Joo-Cheol;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.31 no.6
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    • pp.437-444
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    • 2006
  • This study was aimed to elucidate the biological function of OD314 (Apin protein), which is related to ameloblast differentiation and amelogenesis. Apin protein, calcifying epithelial odontogenic (pindborg) tumors (CEOTs)-associated amyloid, were isolated from CEOTs, and has similar nucleotide sequences to OD314. We examined expression of the OD314 mRNA using in-situ hybridization during tooth development in mice. Expression of OD314 and several enamel matrix proteins were examined in the cultured ameloblast cell line up to 28 days by reverse transcription-polymerase chain reaction (RT-PCR) amplification. After inactivation and over-expression of the OD314 gene in ameloblast cell lines using U6 vectordriven RNA interference and CMV-OD314 construct, RT-PCR were performed to evaluate the effect of the OD314 during amelogenesis. The results were as follows: 1. In in-situ hybridization, OD314 mRNAs were more strongly expressed in ameloblast than odontoblast. 2. When ameloblast cells were cultured in the diffcrentiation and mineralization medium for 28 days, the tuftelin mRNA expression was maintained from the beginning to day 14, and then gradually decreased to day 28. The expressions of amelogenin and enamelin were gradually decreased according to the ameloblast differentiation. 3. Inactivation of OD314 by U6-OD314 siRNA construct down-regulated the expression of OD314, MMP-20, and tuftelin, whereas over-expression of OD314 by CMV-OD314 construct up-regulated the expression of OD314 and MMP-20 without change in tuftelin. These results suggest that OD314 is considered as an ameloblast-enriched gene and may play the important roles in ameloblast differentiation and mineralization.

THE EFFECT OF BMP REGULATED SMAD PROTEIN ON ALKALINE PHOSPHATASE GENE EXPRESSION (Smad에 의한 alkaline phosphatase 유전자의 발현 조절기전)

  • Kim, Nan-Jin;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.28 no.2
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    • pp.238-246
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    • 2001
  • Bone morphogenetic proteins(BMPs), members of the transforming growth factor $\beta$(TGF-$\beta$) superfamily were first identified as the factors that induce ectopic bone formation in vivo, when implanted into muscular tissue. Especially BMP-2 inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells. In the molecular mechanism of the signal transduction of TGF-$\beta$ and related factors, intracellular signaling proteins were identified as Smad. In previous study, it has been reported that Smad 1 and Smad 5, which belong to the R-Smad family mediate BMP signaling, were involved in the induction of osteoblast differentiation in C2C12 cells. To understnad the role of Smads involved in osteogenic transdifferentiation in C2C12 cell, in present study, after we stably transfected C2C12 cells with each. Smad(Smad 1,Smad 5) expression vector, cultured for 3 days and stained for alkaline phophatase activity. ALP activity positive cells appeared in the Smad 1, Smad 5 stably transfected cell even in the abscence of BMP. After transiently co-transfected C2C12 cells with each Smad expression vector and ALP promoter, it was examined that Smad 1 and Smad 5 expression vector had increased about 2 fold ALP promoter activity in the abscence of BMP. These result suggested that both Smad 1 and Smad 5 were involved in the intracellular BMP signals which induce osteoblast differentiation in C2C12 cells. The effect of BMP on C2C12 cells with Smad 1, Smad 5 transfected were studied by using northern blot analysis. the treatment of BMP upregulated ALP mRNA level in three groups, especially upregulation of ALP was larger in Smad 1, Smad 5 transfected cell than control group. Pretreatment with cycloheximide($10{\mu}g/ml$), a protein synthesis inhibitor resulted in blocking the ALP gene expression even in BMP(100ng/ml) treated cell. These results suggested that Smad increased the level of ALP mRNA via the synthesis of a certain transcriptional regulatory protein.

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Clinical Characteristics and Abnormal p53 Expression of Lung Cancer Associated with Multiple Primary Cancer (다발성 악성종양에 동반된 폐암의 임상 특징과 변이형 p53 발현)

  • Shin, Chang-Jin;Park, Hye-Jung;Shin, Kyeong-Cheol;Shim, Young-Ran;Chung, Jin-Hong;Lee, Kwan-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.331-338
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    • 1999
  • Background: Nearly 10% of cancer patients will develop a second primary cancer within ten years after surgical removal of the primary tumor. The detection of risk factors for developing multiple primary tumors would be important This study was conducted to evaluate the clinical characteristics and abnormal p53 expression of lung cancer associated with multiple primary cancer(MPC). Method: Clinical characteristics and abnormal p53 expression were compared between 20 cases of lung cancer(NSCLC ; 16 cases, SCLC ; 4 cases) associated with MPC and 26 cases of primary non-small cell lung cancer. Result: MPC associated with lung cancer was gastric cancer(8), lung cancer(2), esophageal cancer(2), colon cancer(2), laryngeal cancer(1), bladder cancer(1), small bowel cancer(l), adrenal cancer(1), hepatocellular carcinoma(1), and breast cancer (1) in order. The clinical stage of primary NSCLC was relatively advanced, but NSCLC associated with MPC was even distribution at each stage. The detected incidences of abnormal p53 expressions were 62.5% in NSCLC associated with MPC and 76.9% in primary NSCLC(p>0.05). Conclusion: There was no difference in abnormal p53 expression between non-small cell carcinoma associated with multiple primary cancer and primary non-small cell carcinoma.

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Effect of Hog Millet Supplementation on Hepatic Steatosis and Insulin Resistance in Mice Fed a High-fat Diet (고지방식이로 유도한 지방간 마우스에서 기장 첨가식이가 지방간 및 인슐린 저항성에 미치는 영향)

  • Park, Mi-Young;Jang, Hwan-Hee;Lee, Jin-Young;Lee, Young-Min;Kim, Jae-Hyun;Park, Jae-Hak;Park, Dong-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.4
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    • pp.501-509
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    • 2012
  • The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. In our previous study, hog millet (HM, $Panicum$ $miliaceum$ L.) water extract showed the highest anti-lipogenic activity among nine cereal types in 3T3-L1 cells. In this study, the effect of hog millet water extract on hepatic steatosis and lipid metabolism in mice fed a high fat diet was investigated. Mice were fed a normal-fat diet (ND), high-fat diet (HFD) or HFD containing 1% or 2% (w/w) HM for 7 weeks. Body weight and food intake were monitored during the study period. Insulin resistance by homeostasis model assessment (HOMA-IR), fasting lipid profile, hepatic fatty acid metabolism-related gene expression determined, and intraperitoneal glucose tolerance test (IGTT) were performed at the study's end. The results indicated that 1% and 2% HM diets effectively decreased liver weights, blood TG and T-cholesterol levels (p<0.05), while the HDL-cholesterol level was increased (p<0.05) compared to HFD-induced steatotsis mice. Hepatic lipogenic-related gene ($PPAR{\alpha}$, L-FABP, and SCD1) expressions decreased, whereas lipolysis- related gene (CPT1) expression increased in animals fed the 2% PME diet (p<0.05). In addition, mice fed 1% or 2% HM diet had markedly decreased IGTT and HOMA-IR, compared to the those of the HFD-induced hepatic steatosis control group (p<0.05). These results indicated that HM inhibited hepatic lipid accumulation by regulating fatty acid metabolism, and suggested that HM is useful in the chemoprevention or treatment of high fat-induced hepatic steatosis and hepatic steatosis-related disorders including hyperlipidemia, glucose sensitivity, and insulin resistance.

Quality and shelf life of sliced root of Platycodon grandiflorum treated by ozon-microbubble-heat shock (오존-마이크로버블-열수 처리한 세절 도라지의 품질 및 저장성)

  • Park, Kyung Min;Lee, Ji Young;Min, So-Ra;Jeong, Moon-Cheol;Koo, Minseon
    • Food Science and Preservation
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    • v.23 no.5
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    • pp.605-613
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    • 2016
  • The quality and shelf life of sliced root of Platycodon grandiflorum (Doraji) treated by ozon-microbubble-heat shock (OMH) were investigated by combining modified-atmosphere packaging [MAP, ($50%O_2+15%CO_2+35%N_2$)]. The study was based on microbiological (total viable bacteria, fungi, Enterobacteriaceae and coliforms numbers), physicochemical and sensory changes. OMH treatment was effective in reducing microbial populations of the sliced Doraji, especially Enterobacteriaceae and coliforms reduced by 2 log CFU/g. However OMH-MAP treatment remained the aerobe and fungi numbers. Regarding the color, OMH-MAP delayed the change of Hunter $b^*$ and the sliced Doraji by OMH-MAP treatment exhibited lower decrease of flavor and overall acceptability compared to those by polypropylene packaging after tap water treatment (Control). The OMH and $50%O_2+15%CO_2$ MAP treatment gave better sensory quality and extended shelf-life for sliced Doraji (~3 days longer shelf-life than Control). Flavor was significantly related to overall acceptability at both Control and OMH-MAP, whereas total coliforms prevalence was associated with overall acceptability at only OMH-MAP. Therefore microbubble-heat shock treatment may improve microbial safety and sliced Doraji by OMH treatment can stored under $50%O_2+15%CO_2$ treatment for up to 7 days. Thus, OMH and MAP treatment may be used in maintaining the storage quality and marketability of sliced Doraji.

Clinical Significance of Plasma TGF-${\beta}_1$ in Coal Workers' Pneumoconiosis (탄광부 진폐증에서 혈장 Transforming Growth Factor-${\beta}_1$의 의의)

  • Kim, Chong-Ju;Lee, Won-Yeon;Hong, Ae-Ra;Shin, Pyo-Jin;Yong, Suk-Joong;Shin, Kye-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.76-83
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    • 2001
  • Background : Coal workers' pneumoconiosis is a fibrotic lung disease resulting from chronic inhalation of coal dust. The precise mechanism of lung fibrosis in coal workers' pneumoconiosis is uncertain. However, a relationship between the stimulation of fibroblast proliferation and collagen production by mediators released from in flammatory and resident lung cells is thought to be a major factor. The transforming growth factor-$\beta$(TGF-$\beta$), a multifunctional cytokine and growth factor, plays a key role in the scarring and fibrotic processes due to its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. To determine the involvement of TGF-$\beta$ in the development of lung fibrosis in coal workers' pneumoconiosis, the TGF-${\beta}_1$ level in plasma was measured in patients with coal workers' pneumoconiosis. Methods : Plasma was collected from 40 patients with coal workers' pneumoconiosis (20 with simple coal workers' pneumoconiosis and 20 with complicated coal workers' pneumoconiosis) and from 10 normal controls. The ELISA method was used to measure the plasma TGF-${\beta}_1$ concentration. Results : Compared to the control group ($0.63{\pm}01.8$ ng/mL), there was no significant difference in the plasma TGF-${\beta}_1$ level in patients with simple coal workers' pneumoconiosis ($0.64{\pm}0.17$ ng/mL) (p>0.05). However, in patients with complicated coal workers' pneumoconiosis the plasma TGF-${\beta}_1$ level ($0.79{\pm}0.18$ ng/mL) was significantly higher than in patients with simple coal workers' pneumoconiosis and the control group (p<0.05). Conclusion : The data suggests that TGF-${\beta}_1$ has some influence in the development of lung fibrosis in coal workers' pneumoconiosis.

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