Razzaque Mohammed S, Kumari Suman, Foster C Stephen, Ahmed A Razzaque
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
Cytokine. 2003 Mar 7;21(5):207-13. doi: 10.1016/s1043-4666(03)00034-6.
Epidermolysis bullosa acquisita (EBA) is a chronic, uncommon, sub-epidermal blistering disease involving the skin and mucous membranes that heals with scar formation and milia. Collagens, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are important components that play an essential role(s) in matrix remodeling during scar formation. However, the possible involvement of these components in EBA-induced scarring is not yet known. In the present study, we examined the expression profile of collagens, collagen-binding heat shock protein 47 (HSP47), MMPs and their inhibitory enzymes, TIMPs, in matrix remodeling during conjunctival scarring. The involvement of TGF-beta1, a fibrogenic factor, was also studied. Compared to the controls, an increased expression of type I collagen, type III collagen and HSP47 was detected in conjunctival biopsy sections of patient with EBA using immunohistochemistry. Similar increase in the expression of type I collagen, type III collagen and HSP47 was noted in conjunctival fibroblasts obtained from the patient with EBA. Up-regulation in the expression of MMP-1 and MMP-14 was also noted in conjunctival fibroblasts isolated from the patient with EBA, while no significant changes in the expression of MMP-3, MMP-8, MMP-9 and MMP-13 were seen. As for TIMPs, conjunctival fibroblasts isolated from the patient with EBA, grown in vitro, exhibited increased expression of TIMP-1, TIMP-2 and TIMP-3, when compared with fibroblasts grown from control conjunctival tissues, although the expression level varies with different molecules of the same family. Additionally, compared to the control conjunctival fibroblasts, an increased expression of TGF-beta1 was detected in fibroblasts isolated from the conjunctival tissues of patient with EBA. This study suggests that there is up-regulation in the production of collagens (type I and III), collagen-binding protein (HSP47), matrix degrading collagenases (MMP-1 and 14), and their inhibitory enzymes (TIMP-1, 2 and 3) during the process of conjunctival matrix remodeling in the patient with EBA. The presented data is preliminary and could serve as a basis for further studies to enhance our understanding about the molecular mechanisms of conjunctival scarring in patients with EBA.
获得性大疱性表皮松解症（EBA）是一种慢性、罕见的表皮下大疱性疾病，累及皮肤和黏膜，愈合后会形成瘢痕和粟丘疹。胶原蛋白、基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）是在瘢痕形成过程中基质重塑中起重要作用的重要成分。然而，这些成分在EBA引起的瘢痕形成中的可能作用尚不清楚。在本研究中，我们研究了胶原蛋白、胶原结合热休克蛋白47（HSP47）、MMPs及其抑制酶TIMPs在结膜瘢痕形成过程中基质重塑中的表达谱。还研究了促纤维化因子转化生长因子-β1（TGF-β1）的作用。与对照组相比，使用免疫组织化学法在EBA患者的结膜活检切片中检测到I型胶原、III型胶原和HSP47的表达增加。从EBA患者获得的结膜成纤维细胞中也观察到I型胶原、III型胶原和HSP47的表达有类似增加。从EBA患者分离的结膜成纤维细胞中还观察到MMP-1和MMP-14的表达上调，而MMP-3、MMP-8、MMP-9和MMP-13的表达未见明显变化。至于TIMPs，与从对照结膜组织培养的成纤维细胞相比，从EBA患者分离的体外培养的结膜成纤维细胞中TIMP-1、TIMP-2和TIMP-3的表达增加，尽管同一家族不同分子的表达水平有所不同。此外，与对照结膜成纤维细胞相比，从EBA患者结膜组织分离的成纤维细胞中检测到TGF-β1的表达增加。本研究表明，在EBA患者结膜基质重塑过程中，胶原蛋白（I型和III型）、胶原结合蛋白（HSP47）、基质降解胶原酶（MMP-1和14）及其抑制酶（TIMP-1、2和3）的产生上调。所呈现的数据是初步的，可为进一步研究提供基础，以加深我们对EBA患者结膜瘢痕形成分子机制的理解。
