Keloid 세포의 Collagen 합성에 대한 Phorbol ester, Okadaic acid 및 Steroid의 작용

김원태,김인산,박낭운,손건영,조준승 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.1

목적 : 이 연구는 Keloid 병변부위와 그 인접부위 그리고 정상부위의 세포에서의 collagen 합성에 대한 phorbol myristate acetate (PMA), okadaic acid (OKA) 및 hydrocortisone (HC)의 영향을 조사·비교 한 것이다. 재료 및 방법 : Keloid 병변부위와 그 인접부위 및 정상피부조직의 작은 절편을 배양하여 섬유아세포가 자라나와 밀생상태로 된후 trypsin 처리로써 섬유아세포만을 분리·계대 배양하였으며, 이 세포배양액에 PMA(100ng/㎖), OKA(10ng/㎖) 또는 HC(1.5μM)틀 부여, 24시간 배양해서 Peterkofsky 등의 방법에 따라 총단백질 및 collagen 합성능을 측정하여 대조군의 그것과 비교하였다. 결과 : Keloid 병변부위 및 그 인접부위의 세포는 정상부위의 세포보다 collagen 합성능이 높았다. 그 중에도 인접부위에서 가장 높았다. 그리고 PMA, OKA 및 HC는 다같이 비슷하게 또 부위에 관계없이 총단백질에 대한 collagen 합성비율을 억제하였다. 이들 약제중 PMA는 주로 noncollagen protein(NCP)을 많이 증가시켰고, OKA는 collagen 합성을 감소시켰다. 결론 : Keloid 병변부위와 그 인접부위의 세포에서 collagen 합성능이 높았다. 그리고 인접부위에선 더욱 PMA, OKA 및 HC에 의해 keloid 병변부위와 정상부위와는 달리 섬유아세포에서의 collagen 합성이 억제되었다. Keloid is a disease characterized by excessive deposition of various connective tissue components, such as collagen. In this study, three types of cells originate from keloid, keloid-adjacent and normal site of keloid patients were used to evaluate collagen synthesis by phorbol myristate acetate (PMA), okadaic acid (OKA) and hydrocortisone (HC). Average collagen synthetic rate by fibroblasts derived form keloid and keloid-adjacent cells was higher than that of normal skin fibroblasts. Keloid-adjacent cell has the most active collagen synthetic rate. PMA, OKA and HC inhibit % collagen synthesis in all three types of cells. In terms of noncollagen protein and collagen synthesis, PMA mainly increased noncollagen protein synthesis on the contrary OKA usually inhibit collagen synthesis in three types of cells. PMA, OKA and HC also inhibit % collagen synthesis in keloid and normal cells derived from the same patient similarity. Also there was no difference % collagen synthesis between keloid cells and keloid-adjacent cells derived from the same patient by three above mensioned reagents. Taken together, collagen synthetic rate was higher in keloid cells, when compared to the normal fibroblasts. In addition, there was no difference between keloid and normal cells in inhibitory effect of PMA, OKA and HC on collagen synthesis.

켈로이드 치료약제가 켈로이드 섬유모세포의 Fibronectin, Transforming Growth Factor-β및 Transforming Growth Factor-β수용체 발현에 미치는 영향

박정민,김석권,이근철,배혜란,나서희,이민혁 대한미용성형외과학회 2005 Archives of Aesthetic Plastic Surgery Vol.11 No.2

Keloids represent a dysregulated response to cutaneous wounding that results in an excessive deposition of extracellular matrix. However, the molecular mechanisms underlying this pathologic deposition of extracellular matrix still remain to be elucidated. In this study, the effects of anti-keloid drugs (triamcinolone, 5-FU, bleomycin, verapamil) on the expression of fibronectin and TGF-β and its receptor in keloid fibroblasts were evaluated in vitro. Human keloid fibroblasts(KFs) and normal human dermal fibroblasts(NHDFs) were isolated from earlobe keloids. Immunoprecipitation and Western blot of fibronectin, ELISA of TGF-β secretion and Western blot of TGF-β receptor were performed using the primary cultured fibroblasts treated with various drugs. TGF-β secretion was increased in keloid fibroblasts compared to NHDFs. TGF-βpromoted fibronectin synthesis in keloid fibroblasts. These results substantiate the hypothesis that the elevated levels of TGF-β play a potential role in keloid pathogenesis. 5-FU suppressed profoundly TGF-β secretion. Triamcinolone and verapamil inhibited significantly fibronectin synthesis and secretion, and also suppressed TGF-β receptor expression in keloid fibroblasts. In conclusion, it is postulated that the combination of low dose of 5-FU and triamcinolone or verapamil may be useful in keloid treatment by the additive effect of different anti-keloid action.

Keloid 세포의 Fibronectin 합성에 대한 Transforming growth factor-β의 영향

구성모,김인산,박낭운,손건영,조준승 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.1

목적 : 이 연구는 keloid가 상처의 치유과정에 발생하는 비후성인 반흔의 일종으로서 결합 조직이 국소적으로 과도하게 축적된 것이 특징이나 원래 부위에만 국한되지 않고 주위조직으로 침범해 가는 특성을 가진데 관점을 두어 환부와 그 인접부 그리고 정상조직에서 얻은 배양 세포에서 결합조직의 한 성분인 fibronection의 합성능을 조사하여 상호 비교하고 또 이 합성에 대한 transforming grown factor-β (TGF-β)의 영향을 조사해 보기로 하였다. 대상 및 방법 : Keloid 병변부 8예, keloid 인접부 4예, 정상조직 4예에서 조직을 채취·배양해서 얻은 섬유아세포를 사용하여 fibronectin 합성능을 조사했다. 또 이에 대한 TGF-β의 영향을 조사하기 위해 세포를 24시간 동안 TGF-β로 처리하였다. Fibronectin의 합성능 측정은 면역침전법에 의하였다. 결과 : Fibronectin의 합성은 병변부 세포에서 정상부위 세포보다 약 1.6배로 많았으며, 인접부위세포에서는 병변부 세포보다 약 1.7배, 정상부위 세포보다 약 2.7배로 많았다. 그리고 TGF-β를 처리한 후의 fibronectin 합성은 처리하지 않았는 대조군에 비하여 정상부위 세포에서는 약 1.8배, 병변부세포에선 약 1.4배로 증가되었으나 인접부위 세포에서는 별로 증가되지 않았다. 결론 : Keloid의 환부는 정상부위에 비하여 세포의 matrix 성분의 하나인 fibronectin의 합성이 활발하며 특히 병변부 주위에서 더욱 활발하였다. Fibronectin의 합성은 TGF-β에 의해 분명히 증가되나 keloid 인접부위에서는 이에 무감작할 정도였다. 이 부위는 여러 인자에 의해 그 합성이 활발하다고 하겠다. Keloids are fibrous, hypertrophic scar reaction that occur secondary to skin injury and tend to recur after excision. Histopathologically there is an overabundace of various connective tissue components such as collagen and fibronectin. Characteristically keloids spread to invade surrounding normal skin beyond the boundaries of the original wound. In this study focusing on this invasion behavior, fibronectin synthesis in the four keloid adjacent fibroblasts as well as in the three normal and eight keloid cells, were determined. The effect of transforming grown factor-β (TGF-β), which is well known as increasing the synthesis of collagen and fibronectin, on the fibronectin synthesis of the above cells was also investigated. Fibronectin was synthesized in keloid cells about 1.6 fold more than in the normal cells, and the fibronectin synthesis in the keloid adjacent cells was about 1.7, and 2.7 folds more than in the keloid and normal cells respectively. Twenty-four hour TGF-β treatment increased fibronectin synthesis in normal cells by about 1.8 fold and in keloid cells by about 1.4 fold. In contrast, adjacent cells showed little response to TGF-β. Above results suggest that adjacent cells are locally under active TGF-β stimulation and thus synthesize more fibronectin than normal or keloid cells and additional stimulation of TGF-β, however, has little effect on adjacent cells.

공동배양실험모델에서 켈로이드 상피세포가 섬유모세포의 TGF-β1 생성에 미치는 영향

박준,강상윤,유영천,양원용 대한성형외과학회 2004 Archives of Plastic Surgery Vol.31 No.4

Keloids represent a pathological response to injury interrupting skin integrity, creating disfiguring scars with no definitive pathophysiology. Transforming growth factor-β1(TGF-β1) has been regarded as one of the pathogenesis of keloids. The purpose of this study is to investigate the influence of keloid keratinocytes on TGF-β1 expression in co-culture system. Recent studies have highlighted the important concept of epithelial- mesenchymal interactions in normal skin biology, and applying this concept to keloids in vitro studies demonstrated significantly increased proliferation of fibroblasts and collagen production in keloid fibroblasts co-cultured with keloid-derived keratinocytes as compared with normal keratinocytes. In this study, normal or keloid fibroblasts in lower chamber were co-cultured with keratinocytes derived either from normal skin or keloid tissue in upper chamber, separated from lower chamber by permeable membrane. Results obtained by ELISA showed equal TGF-β1 expression when keloid fibroblasts were co- cultured with keloid keratinocytes, as compared with the normal keratinocytes at 24,48 hours, but significantly higher expression at 72 hours(p=0.0358). RT-PCR demonstrated that the TGF-β1 expression level was not significantly related to the level of mRNA encoding TGF-β1. These results suggest that overlying keloid keratinocytes play an important role in inducing high level of TGF-β1 expression in keloid by paracrine effect or epithelial-mesenchymal interaction.

Keloid세포의 Collagen합성에 관한 연구

박혜경,박낭운,이병헌,최제용,김인산,조준승 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.2

목적 :이 연구의 목적은 keloid가 점점 그 주위조직으로 침범하는 성질이 있는 것에 착안하여 keloid 중심부위와 그 인접부위 그리고 정상부위 조직에서의 collagen 합성능을 측정하여 상호비교 해보는데 있다. 재료 및 방법 : 7예의 keloid 섬유아세포와 3예의 keloid 인접부위 섬유아세포 그리고 5예의 정상부위 섬유아세포를 배양하여 Peterkofsky씨등의 방법^13)에 따라 collagen 합성능을 측정하였다. 해체와 배양조건에 따른 차이를 배제하기 위하여 한 환자로부터 동시에 각 부위의 조직을 동시에 얻어 동시에 섬유아세포를 배양하였다. 결과 : Collagen 합성능의 평균값은 정상조직보다 keloid 부위에서 훨씬 높았으며 또한 keloid 부위보다 그 인접부위에서 더욱 높았다. 결론 : 섬유아세포에서의 collagen 합성능은 정상부위, keloid 부위 및 그 인접부위 순으로 더욱 높았다. 이것은 keloid 환부주위에 국소적으로 작용하는 인자들이 존재하여 이들에 의해 keloid 주위조직이 자극을 받아 collagen 합성능이 증가하게 됨을 시사한다. Keloids are predominantly fibrous skin tumors that take the form of firm, variably pruritic or tender growths near the site of an injury. Histopathologically they are ricd in various connetive tissue components, such as collagen. In this study, the collagen synthesis by fibroblasts derived from keloid, keloid-adjacent area and normal skin was analyzed. Six keloid fibroblast cell lines out of 7 demonstrated increased collagen synthesis and one showed collagen synthetic rate that was within the control limits. One keloid fibroblast cell and one normal fibroblast cell were cultured from a patient, and when their collagen synthetic rates were compared with each other it resulted in that keloid cells showed a higer synthetic rate than normal cells. Three keloid-adjacent fibrolast cell lines showed markedly incerased collagen synthesis than their corresponding keloid cell lines which were derived from the same patients. Taken together, these results suggest that in keloid lesion, there might be local factors which stimulate surrounding fibroblasts to synthesize excessive collagen.

Nickel allergy in patients with ear keloid

( Yeona Kim ),( Kihyuk Shin ),( Woo-il Kim ),( Min-young Yang ),( Won-ku Lee ),( Hoon-soo Kim ),( Hyun-chang Ko ),( Byung-soo Kim ),( Moon-bum Kim ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

Background: Keloids are thought to be the result of abnormal wound healing related to inflammation on the reticular dermis. Dermatologists often encounter patients with ear keloid. However, there is a lack of research on factors that can affect the development of ear keloids. Objectives: To investigate the relationship between nickel allergy and ear keloids. Methods: A questionnaire survey and patch test was conducted on patients who attended department of dermatology at Pusan national university hospital between October 2016 and November 2018. Results: A total of 17 patients (mean onset age 21.4) with ear keloids were included. All 17 patients were female. All patients had history of piercing on keloid site and the piercings were made of alloy. In 9 patients (52.9%), keloid was dominant on the posterior surface of the ear noted keloid. Before keloid formation, 10 patients (58.8%) reported inflammatory signs and most patients (88.2%) complained about itching or pain. Half of patients (58.8%) presented positive result of nickel patch test and 4 patients showed positive result of cobalt. Conclusion: In a previous Korean studies, 34% subjects had nickel allergy, while this study found a higher percentage of patients with nickel allergy. Keloid dominant on the posterior surface could explain by earring’s metallic backs made of nickel. These results suggest not only mechanical force but inflammation induced by metal allergy like nickel could contribute the keloid formation.

10년간 단일 기관에서의 귀 켈로이드 임상 및 역학 연구

김충재 ( Choong Jae Kim ),최훈 ( Hoon Choi ),나찬호 ( Chan Ho Na ),신봉석 ( Bong Seok Shin ),김민성 ( Min Sung Kim ) 대한피부과학회 2021 대한피부과학회지 Vol.59 No.1

Background: Keloids are benign dermal fibrous growths associated with excessive collagen deposition that usually occurs after trauma or surgery. To date, the clinical features and epidemiology of ear keloids have not been comprehensively investigated. Objective: We investigated the epidemiology and clinical characteristics of ear keloids in Koreans. Methods: We retrospectively investigated Koreans diagnosed with ear keloids by dermatologists at the Department of Dermatology, Chosun University Hospital, between January 2010 and December 2019. Results: The study included 95 patients with 120 ear keloid lesions (mean size of lesions 1.12×1.45 ㎠). Based on the ear anatomy, the keloids were observed at the following sites: the helix in 61 (50.8%) patients, the earlobe in 37 (30.8%) patients, antihelix in 10 (8.3%) patients, scapha in 3 (2.5%) patients, and the postauricular region in 9 (7.5%) patients. Among the keloids evaluated, 67 (55.8%), 36 (30.0%), 9 (7.5%), and 8 (6.7%) were categorized as lobular, dumb-bell, button, and wrap-around types, respectively. Most (75%) keloids were located on the posterior surface of the ears. Notably, 26 patients had a family history of keloids, which was significantly correlated with the development of keloids at other sites (p<0.001). Conclusion: The helix was the most common site of involvement, and lobular keloids represented the most common variety of keloids observed in this study. Keloids occurred most frequently on the posterior surface of the ears and were bigger at these sites. Patients with a family history of keloids were significantly more likely to develop keloids in areas other than the ears. (Korean J Dermatol 2021;59(1):8∼14)

켈로이드의 병변내 절제술 치료에 대한 연구

남재희 ( Jae Hui Nam ),최영준 ( Young Jun Choi ),김태환 ( Tae Hwan Kim ),이가영 ( Ga Young Lee ),박수홍 ( Soo Hong Park ),김원석 ( Won Serk Kim ),김계정 ( Kea Jeung Kim ) 대한피부과학회 2009 대한피부과학회지 Vol.47 No.6

Background: Keloid is one of the most frustrating clinical problems in wound healing. There are numerous treatments for keloids such as surgical excision, steroid injection, radiation therapy, laser, silicone gel application and so on. Surgical excision of a keloid is generally not accepted as a first treatment of choice. However, there have been many reports of successful cosmetic results from specialized surgical treatments such as intra-lesional/intra-marginal excision with or without post surgical adjuvant treatments. Objective: The aims of this study areto evaluate the effectiveness of intralesional excision of keloids, the optimal surgical conditions and the proper adjuvant therapy after surgery. Methods: We analyzed the medical records and clinical photographs of 20 patients who underwent intra-lesional excision of their keloids and who had regular follow-ups for at least for 3 months. The clinical outcomes were assessed by three independent physicians based on their interpretation of the photographs before and after surgery with using a global assessment 5 point scale that ranged from bad, poor, fair and good to excellent. Results: General surgical outcomes after intra-lesional excision: the average improvement score was 4.05 after intra-lesional excision and adjuvant therapy. The average improvement score after intra-lesional excision was 4.71 for ear keloids and 2.83 for keloids in other areas (p=0.000). The average improvement score after intra-lesional excision was 5 for earlobe keloids and 4.42 for ear-helix keloids (p=0.014). The average improvement score was 3.92 for the steroid intra-lesional injection and topical silicone gel combination treatment group after intra-lesional excision and the average improvement score was 4.29 for the single topical silicone gel treatment group (p=0.858). Conclusion: Although surgery is not a first treatment of choice for the management of keloids, large recalcitrant keloids need massive surgical removal for faster clinical results. In this study, we found that surgery, and especially intra-lesional excision, is not an absolute contraindication for treating keloids and this is sometimes considered as the first treatment of choice, and especially for ear keloids. However, a more careful surgical approach is necessary for the case of keloids that develop in other areas. Further studies about the optimal surgical indications for keloids and the recommended adjuvant therapy after surgery are necessary. (Korean J Dermatol 2009;47(6):641∼648)

Treatment of ear keloids by surgical excision combined with intralesional corticosteroid injections and pulsed dye laser therapy

( Sang Myung Park ),( Joong Yoon Choi ),( Ye Jin Lee ),( Bark Lynn Lew ),( Woo Young Sim ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Keloids are hard hyperproliferation of dermal collagen resulting from abnormal healing response to injury. The ear is one of the most frequent locations for keloid formation. Numerous treatments have been utilized for keloid, but treatment options are still controversial. Objectives: We assess the efficacy of excision combined with postoperative intralesional injection (ILI) of triamcinolone acetonide (TA) and pulsed dye laser (PDL) therapy for treating earlobe and helix of the auricle keloids. Methods: A retrospective study was performed between January 2008 and December 2017. A total of 18 patients had a surgical excision followed by postoperative ILI of TA every 1 month for several months. Of these, 8 patients received additional PDL therapy at the sometimes. Treatment efficacy was assessed visually using a 3-item scale depending on the reduction in the keloids. Results: Eighteen patients with a total of 21 keloids were included. After the surgery, ILI of TA were given 2 to 13 times. Eight patients received an additional 1 to 12 PDL therapy at the sametimes. In patients treated with ILI of TA alone, 8 keloids showed significant or moderate improvement (60%) and 5 keloids recurred (40%). However in patients treated with ILI of TA and PDL therapy, 7 keloids show significant improvement (87%) and only 1 keloid recurred (13%). Conclusion: The combination of surgical excision and ILI of TA and PDL therapy can be considered for the first line therapy in patients with ear keloids.

Epidermal Growth Factor (EGF)-Like Repeats and Discoidin I-Like Domains 3 (EDIL3): A Potential New Therapeutic Tool for the Treatment of Keloid Scars

류연희,이윤재,김기주,이수진,한유나,이종원 한국조직공학과 재생의학회 2017 조직공학과 재생의학 Vol.14 No.3

In keloids, the mechanism underlying the excessive accumulation of extracellular matrix after injury of the skin is unclear, and there is no effective treatment because of the incomplete understanding of their pathogenesis; thus, a high recurrence rate is observed. We studied a new marker of keloids to determine a new treatment strategy. First, the keloid gene expression profile (GSE44270) was analyzed (downloaded from the Gene Expression Omnibus database) and the new keloid marker candidate, epidermal growth factor (EGF)-like repeats and discoidin I-like domains 3 (EDIL3) which were upregulated in keloid samples was identified. Knockdown of EDIL3 is known to suppresses angiogenesis by downregulating relevant inhibitory factors that can limit the supply of survival factors to tumor cells from the circulation via the vascular endothelial cells. In keloids, the mechanism of action of EDIL3 may be similar to that in tumors; the inhibition of apoptosis in tumor cells via a reduction in the apoptosis of blood vessels by upregulating an angiogenic factor. To determine whether EDIL3 is involved in keloid formation, we performed knockdown of EDIL3 in keloid fibroblasts in vitro by transfection with anti-EDIL3 small interfering RNA (via microporation). EDIL3 was upregulated in keloid fibroblasts compared with normal fibroblasts in collagen type I, II and III. Our results indicate the control of EDIL3 expression may be a new promising treatment of keloid disease also the molecular targeting of EDIL3 may improve the quality of treatment and reduce the formation of keloids.