• 한국식품영양과학회지
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• 제39권10호
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• pp.1452-1458
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• 2010

상처치료 과정 중 ginsenoside Rg1(5,000 ppm, 10,000 ppm) 처리에 의한 효력을 평가하기 위해 SD rats의 등쪽 피부에 biopsy punch를 이용한 4개의 창상을 유발 후, 이 과정에서 일어나는 피부조직의 변화를 관찰하였다. 상처에 Rg1의 도포로 인해 창상치료과정이 활발해짐을 관찰할 수 있었다. Rg1을 처리한 군에서 절개된 상처의 표피화와 수축이 더 빨라졌고 창상면적에 있어서도 양성대조군인 시판연고 도포군과 비교하여 유의하게 줄어들었다. 염색한 조직의 현미경 관찰 결과에서는 정상대조군에서 볼 수 있는 완전한 상피층은 찾을 수 없었으나 Rg1 처리군에서 모낭과 신생혈관이 관찰되었고 상피층의 회복조짐도 관찰되었다. 병변의 TGF-$\beta$ 및 VEGF의 발현량을 조사한 결과 Rg1의 도포에 의하여 더 많은 VEGF의 발현을 유도하고 TGF-$\beta$의 활성화를 차단하여 반흔 형성을 감소시켰다. 이러한 결과를 종합하여 Rg1은 흰쥐의 외과적 창상에 치료효과가 있다고 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권5호
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• pp.650-657
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• 2018

Objective: The study investigated the biological functions and mechanisms for controlling cashmere growth of Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) and decorin (DCN) genes. Methods: cDNA library of Liaoning cashmere goat was constructed in early stages. OCIAD2 and DCN genes related to cashmere growth were identified by homology analysis comparison. The expression location of OCIAD2 and DCN genes in primary and secondary hair follicles (SF) was performed using in situ hybridization. The expression of OCIAD2 and DCN genes in primary and SF was performed using real-time polymerase chain reaction (PCR). Results: In situ hybridization revealed that OCIAD2 and DCN were expressed in the inner root sheath of Liaoning cashmere goat hair follicles. Real-time quantitative PCR showed that these genes were highly expressed in SF during anagen, while these genes were highly expressed in primary hair follicle in catagen phase. Melatonin (MT) inhibited the expression of OCIAD2 and promoted the expression of DCN. Insulin-like growth factors-1 (IGF-1) inhibited the expression of OCIAD2 and DCN, while fibroblast growth factors 5 (FGF5) promoted the expression of these genes. MT and IGF-1 promoted OCIAD2 synergistically, while MT and FGF5 inhibited the genes simultaneously. MT+IGF-1/MT+FGF5 inhibited DCN gene. RNAi technology showed that OCIAD2 expression was promoted, while that of DCN was inhibited. Conclusion: Activation of bone morphogenetic protein (BMP) signaling pathway up-regulated OCIAD2 expression and stimulated SF to control cell proliferation. DCN gene affected hair follicle morphogenesis and periodic changes by promoting transforming growth $factor-{\beta}$ ($TGF-{\beta}$) and BMP signaling pathways. OCIAD2 and DCN genes have opposite effects on $TGF-{\beta}$ signaling pathway and inhibit each other to affect the hair growth.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.871-888
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• 1997

연구배경 : 특발성 폐 섬유화확 병인론으로 폐포염과 폐에 침윤한 염증세포 및 폐 조직자체의 실질세포들이 성장인자를 포함한 다양한 cytokine을 분비하여 실질조직을 구성하는 세포에 손상을 야기함으로써 종국에는 섬유화를 초래하는 것으로 이해하고 있다. 그러나 이들에 대한 개괄적인 연구가 부족하고 매개체 각각에 대한 단편적인 논문들뿐이어서 본 연구에서는 BLM유도 폐 손상및 섬유화의 발생기전에 있어서 IL-1, IL-6, TNF-$\alpha$와 TGF-${\beta}_1$, PDGF, bFGF들의 역할을 규명하고자 하였다. 방 법 : Wistar백서를 정상대조군, BLM투여군, BLM과 비타민 E병합투여군으로 나누었고 BLM 투여후 제 1, 2, 3, 4, 5, 7, 14, 21, 28일에 각각 도살한 다음 기관지폐포 세척술을 시행하여 시기별 총 세포수, 세포 구성성분비율을 살펴보았고 TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6, TNF-$\alpha$에 대한 면역조직화학 염색, TGF-${\beta}_1$ mRNA에 대한 동소보합결합검사를 시행, 각 매개체의 생성소, 발현분포 및 정도를 분석하였다. 결 과 : BLM 투여후 1~7 일에 중성구와 기관지상피세포에서 생성된 IL-1, IL-6는 폐손상부위로 원하는 것으로 생각되며 7일이내에 기관지상피세포에서의 IL-1, IL-6 의 양성발현은 기관지상피세포가 BLM 유도 폐 섬유화시 기도주변에서 일어나는 염증 및 면역반응을 항진 및 유지시키는 간접증거로 생각된다. TNF-$\alpha$는 BLM투여후 1~5일에는 기관지상피세포, 중성구가 주생성소로 폐손상부위로의 염증세포의 이동에 주요역할을 하는 것으로 생각되며 7~28일에는 대식세포가 주생성소로서 섬유화를 촉진시키는 것으로 생각된다. TGF-${\beta}_1$은 기관지 상피세포, 대식세포가 주생성소로서 섬유모세포가 표적세포로 생각되며 섬유모세포가 세포외 기질을 생성하도록 자극하고 대식세포에서 유리된 PDGF와 함께 섬유모세포의 증식을 자극한다. 대식세포 및 섬유모세포에서 유리된 bFGF는 TGF-${\beta}_1$과 함께 교원질과 같은 세포외기질의 생성을 자극하는 것으로 여겨진다. 비타민 E와 BLM 병합투여군의 경우 6가지 성장인자 및 cytokine의 발현세포는 같았으나 발현세포수는 극히 미미하였고 trichrome염색상 섬유화도 미약하였다. 결 론 : BLM으로 인한 혈관내피 및 폐포상피세포 손상이후 침윤한 중성구 및 기관지 상피세포가 IL-1, IL-6, TNF-$\alpha$를 분비하여 BLM투여 1~7 일에 많은 수의 중성구를 동원하도록 유도하며 이들이 유리하는 다양한 효소 및 산소유리기가 폐의 정상구조를 파괴하여 섬유화를 시작하게 하는 것으로 생각한다. 손상이 진행됨에 따라 BLM투여 7~28 일에 대식세포가 유리하는 TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$는 섬유모세포를 자극, 이들의 증식을 유도하고 또한 세포외기질의 생성증가를 유도하여 폐 섬유화를 진행시키는 것으로 사료되며 TNF-$\alpha$는 BLM투여후 전 기간에 걸쳐 다수의 세포에서 발현된 점으로 미루어 섬유화에 있어서 TGF-${\beta}_1$ 못지않은 중요한 역할을 하는 것으로 여겨진다. 또한 비타민 E가 BLM유도 폐 손상으로 인한 폐 섬유화의 정도를 감소시키는 것으로 생각한다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.153-159
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• 2009

We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-${\beta}$ (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-${\beta}$ in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.

• IMMUNE NETWORK
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• 제5권4호
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• pp.215-220
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• 2005

Background: Transforming growth factor-${\beta}$ (TGF-${\beta}1$) directs class switch recombination (CSR) to IgA isotype, which is a predominant antibody in mucosal surfaces. Although IgA is preferentially committed in mucosal lymphoid tissues, it is not definitely established whether hallmarks of IgA CSR such as IgA germ-line transcripts (GLT ${\alpha}$), post-switch transcripts (PST ${\alpha}$) and circle transcripts (CT ${\alpha}$) are readily expressed in such tissues. Therefore, we compared the expression of these transcripts among mouse Peyer's patches (PP), mesenteric lymph nodes (MLN), and spleen. Methods: Levels of GLTs, PSTs and CTs were measured by RT-PCR in isolated PPs, MLNs and spleen cells. Results: GLT ${\alpha}$ and PST ${\alpha}$ were well expressed in PP and MLN cells but in spleen cells. Similar patterns were observed in the expression of GL ${\gamma}$2b and PST ${\gamma}$2b. On the other hand, these transcripts were only inducible in spleen cells upon stimulated with LPS and TGF-${\beta}1$. In addition, CT${\alpha}$ and CT${\gamma}$2b were detected in PP cells. Conclusion: PP B cells readily express IgA GLT, PST, and CT. Overall expression patterns of these transcripts were similar in MLN cells. Thus, these results suggest that microenvironment of PP and MLN influences spontaneous IgA CSR, which lacks in systemic lymphoid tissues such as spleen.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제35권2호
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• pp.73-81
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• 2013

Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

• Clinical and Experimental Pediatrics
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• 제62권3호
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• pp.95-101
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• 2019

Purpose: Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor $(TGF)-{\beta}1$, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model. Methods: Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed. Results: Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5. Conclusion: Losartan treatment reduced expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis.

• 생명과학회지
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• 제33권3호
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• pp.234-241
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• 2023

최근 세계 여러 나라에서 대마초 및 대마제품을 합법화하고 대마를 이용한 다양한 치료법에 대한 연구가 활발히 진행되고 있다. 그러나 대마에는 생물학적 효과가 아직 확립되지 않은 여러 화합물들이 포함되어 있다. 본 연구에서는 인간 모유두 세포(HDPC)의 모발 성장에 대한 칸나비디올(CBD)의 효과를 조사하였다. 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) 및 2,2-diphenyl-1-picrylhydrazyl (DPPH) 라디칼 소거 분석법을 활용하여 CBD의 항산화 활성을 측정하였다. 모유두 세포에서 CBD의 세포생존률은 WST-1 분석법으로 측정하였다. CBD 처리에 의한 모유두 세포에서 모발 성장과 관련된 인자의 발현은 real-time PCR 및 western blot으로 측정하였다. CBD의 항산화 활성 측정결과, DPPH 및 ABTS 자유 라디칼 소거 활성의 IC50 값은 각각 15.46±0.24 μM 및 13.90±0.06 μM으로 뛰어난 활성 산소 제거능을 나타냈다. CBD 처리군은 대조군에 비해 세포 증식이 증가하는 경향을 나타냈다. 또한 모유두 세포에서 Real-Time PCR과 Western blotting을 통해 모발 성장 관련 인자를 측정한 결과, CBD 처리로 인하여 성장 관련 인자들이 증가하는 것으로 나타났다. 종합적으로, 항산화 활성이 높은 CBD는 모유두 세포에서 세포 증식을 증가시키고 모발 성장 관련 인자들을 긍정적으로 조절합니다. 이러한 결과는 CBD가 탈모증에 대한 잠재적으로 활용될 수 있음을 시사한다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권3호
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• pp.169-174
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• 2002

Purpose: Irradiation in the oral cancer patients causes early and late complications such as intraoral mucositis and fibrosis, with a various expression of GM-CSF and TGF-${\beta}1$. The purpose of this study was to investigate the production of GM-CSF and TGF-${\beta}1$ by the irradiated human gingival fibroblasts cultivated with lipopolysaccharide. Materials and Methods: Irradiated (total dose, 60 Gy) human gingival fibroblasts were incubated with LPS. Culture supernatants that were collected at 24, 48, and 72 hours were assessed for GM-CSF and TGF-${\beta}1$ by enzyme-linked immunosorbent assay. Results: 1. GM-CSF production in nomal gingival fibroblasts was increased with incubation time, but decreased with incubation time in irradiated gingival fibroblasts. GM-CSF production in both normal and irradiated gingival fibroblasts induced with LPS was higher than the control. 2. TGF-${\beta}1$ production in normal gingival fibroblasts was decreased after 24 hours, but, it was increased until 48 hours in irradiated gingival fibroblasts. TGF-${\beta}1$ production in normal gingival fibroblasts exposed with LPS was higher than the control. Conversely, It was lower than the control in irradiated gingival fibroblasts exposed with LPS. Conclusion: This indicates that irradiation in gingival fibroblasts may play an important role in radiation-induced intraoral mucositis and fibrosis. However, LPS decreases the production of TGF-${\beta}1$ in the irradiated gingival fibroblasts.

• 한국식품영양과학회지
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• 제43권3호
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• pp.374-380
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• 2014

본 연구에서는 야관문 추출물의 마우스 대식세포에 대한 항염증 활성과 창상유발 동물실험 모델을 통한 창상치유 효과를 조사하였다. RAW264.7 세포에서 야관문 추출물은 0.2 mg/mL 이하 농도에서 세포생존에 영향을 주지 않았으며, 염증반응이 활성화된 대식세포에 대해 농도 의존적으로 유의적인 NO 생성 감소를 나타내었다. 창상유발 동물실험 모델에서 야관문 추출물을 함유한 화장품 조성물의 창상치유효과에 대해 육안적으로 관찰한 결과, SCO군과 CCO군보다 야관문 추출물을 함유한 SSP군에서 약 20~30% 빠른 상처면적 감소 효과를 나타내었으며, 반흔 크기 역시 약 12% 작게 형성되었다. 또한 SSP군 조직의 외피와 진피 재생회복속도가 빨라진 것을 Masson's trichrome 염색을 통해 확인할 수 있었으며, VEGF 및 TGF-${\beta}1$ 유전자 발현이 SCO군과 비교 시 각각 감소 및 증가하였다. 이러한 결과는 야관문 추출물이 항염증 및 교원질 생성 유도를 통한 조직재생 활성에 기여하여 창상치유 속도를 가속화하고 반흔 면적을 감소시킬 수 있는 피부 창상치유와 관련한 코스메슈티컬 소재로써 산업적 활용이 가능함을 보여준다.