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Collagen type XII degradation by MMP12

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reactome.org2025-03-23 收录
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Collagen type XII is a member of the fibril-associated collagens with interrupted triple helices (FACIT) group, thought to be bound to the surface of interstitial collagen fibrils (Keene et al.1991). It has only one alpha chain type, with two collagenous (Col1 and Col2) and three noncollagenous domains (NC1-NC3). Whereas the collagenous and the NC1 and NC2 regions are short, the NHE-terminal NC3 is a huge trimeric domain (Yamagata et al. 1991, Wälchli et al. 1993). Collagen XII may enhance the stability of connective tissues by bridging collagen fibrils (Nishiyama et al. 1994, Bader et al. 2009). It may be a stress response molecule, directly influenced by stretch and shear stress. Expression of COL12A1 is directly stimulated by mechanical forces (Flück et al. 2003, Jin et al. 2003, Arai et al. 2008). Expression is predominantly in bone, suggesting involvement of type XII collagen in the regulation of osteoblasts and cell interactions. Transgenic type XII collagen-null mice have skeletal abnormalities. They have decreased bone matrix deposition and delayed maturation. Compared with controls, Col12a knockout osteoblasts are disorganized, being less polarized with disrupted cell-cell interactions, decreased connexin43 expression and impaired gap junction function (Izu et al. 2011).<br><br>MMP12 can cleave collagen XII (Didangelos et al. 2011).

胶原XII型属于纤维相关胶原中断三螺旋(FACIT)家族,据信其与间质胶原纤维表面相结合(Keene等,1991)。该蛋白仅含有一个α链型,由两个胶原结构域(Col1和Col2)和三个非胶原结构域(NC1-NC3)组成。其中,胶原结构域及NC1和NC2区域相对较短,而NHE端部的NC3区域则构成一个庞大的三聚体结构域(Yamagata等,1991,Wälchli等,1993)。胶原XII型可能通过连接胶原纤维来增强结缔组织的稳定性(Nishiyama等,1994,Bader等,2009)。它可能是一种应激反应分子,直接受到拉伸和剪切应力的影响。COL12A1的表达受到机械力的直接刺激(Flück等,2003,Jin等,2003,Arai等,2008)。其表达主要在骨骼中,表明胶原XII型在成骨细胞调节及细胞相互作用中发挥作用。胶原XII型基因敲除的转基因小鼠表现出骨骼异常,包括骨基质沉积减少和成熟延迟。与对照相比,Col12a基因敲除的成骨细胞排列紊乱,极性降低,细胞间相互作用受损,connexin43表达减少以及缝隙连接功能受损(Izu等,2011)。MMP12能够切割胶原XII型(Didangelos等,2011)。
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该数据集聚焦于胶原蛋白XII型被MMP12降解的研究。胶原蛋白XII型是FACIT组的一员,在骨骼中表达,参与结缔组织稳定和机械应力响应,其缺失会导致骨骼异常。数据集强调了MMP12能够降解胶原蛋白XII型,揭示了其在生物过程中的潜在作用。
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