| 摘要: | 蟹足腫(keloid)與肥厚疤(hypertrophic scar, HS)是臨床上常見的不正常性的疤痕。大約10%之台灣學童在打了卡介苗之後發生蟹足腫。蟹足腫的治療至今仍未令人滿意，因此研究了解蟹足腫的致病機轉才能研發新的藥物來治療。
我們比較蟹足腫與肥厚疤其病理組織學參數變化和a-平滑肌肌動蛋白(a-smooth muscle actin, a-SMA)情形。我們比較各種病理變化的結果顯示keloidal collagen對蟹足腫具診斷性，但僅見於60%之病灶。蟹足腫及肥厚疤兩者各有45%和70%之病灶?SMA有明顯的表現，所以a-SMA之表現程度不具鑑別診斷之價值。
TGF-β1是強的誘發纖維化的細胞素，而且可以誘導纖維母細胞a-SMA表現，對於蟹足腫致病機轉扮演一個關鍵角色。IFN-g和TGF-b1的作用是相反的。一般認為蟹足腫是 TGF-β可能與量過多或不正常反應所導致。我們比較這兩種細胞激素對蟹足腫、肥厚疤及正常組織培養的纖維母細胞a-SMA表現的影響。TGF-β1對三組纖維母細胞a-SMA的表現皆有很強的刺激作用；在先後加入TGF-β1、IFN-γ處理，結果我們發現IFN-γ可抑制a-SMA的表現，但對蟹足腫纖維母細胞(keloid fibroblast, KF)及和肥厚疤纖維母細胞(hypertrophic scar fibroblast, HSF)的抑制效果較弱。KF是唯一在沒有TGF-b1刺激的情況下，就會表現a-SMA的細胞。我們懷疑這些現象是由於KF本身調高TGF-b1 autocrine的效應所致。這些鳥巢狀細胞在蟹足腫的致病原因和蟹足腫膠原中所扮演的角色，以及它是否可以成為蟹足腫的標幟，仍需做進一步的研究。
腎素－血管緊縮素系統(renin-angiotensin system, RAS)中，血管緊縮素II (angiotensin II, Ang II)在高血壓、腎臟及心臟纖維化扮演重要的角色。RAS在人類皮膚亦有表現，也可能在傷口癒合扮演一個角色。所以我們想探討在蟹足腫、正常疤痕組織及正常皮膚RAS的表現情形。在免疫組織染色部份，只有血管緊縮素受體I (angiotensin I receptor, AT1)有表現。在RAS基因部份，三種纖維母細胞之基因皆有表現，但AT1在KF之表現比正常纖維母細胞(normal fibroblast, NF)稍低。這些結果不支持RAS在蟹足腫與肥厚疤的致病機轉當中可能扮演重要的角色。
Keloid and hypertrophic scar (HS) are two common scarring disorders, resulting from abnormal responses to wounding. About 10% of the Taiwan teenagers who received BCG vaccination developed keloid. Various treatments, though effective, are not satisfactory.
We compared various histological features and the expression of a-SMA in keloid and HS, and confirmed the diagnostic value of keloidal collagen, but it was only found in 60% of keloid specimens. a-SMA expression was found in both HS (70%) and keloid (45%), thus it would not be a differentiating marker.
TGF-β1 is profibrotic and can induce a-SMA expression in fibroblasts. It plays a major role in the pathogenesis of keloids. INF-g is antifibrotic and exerts effects opposite to TGF-β1. It has been suggested that there may be excess production or abnormal sensitivity to TGF-β1 in keloids. We compared the effect of TGF-β1 and INF-g on the expression of a-SMA in cultured normal, HS and keloid fibroblasts. The expression of a-SMA was strongly induced by TGF-β1 in all fibroblasts. The stimulation effect of TGF-β1 was suppressed by INF-g with sequential treatment with TGF-β1 and INF-g, but the suppression was to a less extent in HS and keloid fibroblasts. Keloid was the only type of scars displayed peculiar bird nest-like cells with constitutional expression of a-SMA. This phenomenon might be due to constitutionally upregulated autocrine effect of TGF-β1 in keloid fibroblasts.
Activation of the rennin-angiotensin system (RAS) and generation of angiotensin II (Ang II) play a role in the pathogenesis of hypertension and renal and cardiac fibrosis. RAS also is expressed in the skin, and may be involved in wound healing and systemic sclerosis. We compared the expression pattern of RAS (Ang II, ACE, AT1, AT2, rennin) in keloids, hypertrophic scars and normal skin. Only AT1 was detected by in the epidermis of all types of specimens, and in some fibroblasts of keloids by immunohistochemistry study. RT-PCR detected expression of mRNA of all components of RAS system in keloid and normal skin and cultured fibroblasts without obvious difference except for keloid fibroblasts, which expressed less AT1, compared with normal fibroblasts. These results do not support a pathogenic role of RAS in keloid/HS formation. |
