Koyama Y, Kusubata M, Yoshiki A, Hiraiwa N, Ohashi T, Irie S, Kusakabe M
Division of Experimental Animal Research, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
J Invest Dermatol. 1998 Dec;111(6):930-5. doi: 10.1046/j.1523-1747.1998.00401.x.
Tenascin-C is a large extracellular matrix glycoprotein characterized by its spatiotemporal expression during embryogenesis, carcinogenesis, and wound healing. Many in vitro studies on tenascin-C have revealed its multifunctional properties; however, disruption of the tenascin-C gene did not reveal any obvious abnormalities during development, and its function in vivo remains unclear. Here, we investigated whether tenascin-C is involved in inflammatory dermatitis in adults by studying chemically induced dermatitis in tenascin-C knockout mice. An epicutaneous application of a hapten, 2,4-dinitrofluorobenzene, to the ear skin of BALB/CA mice resulted in inflammation and induced the expression of tenascin-C. In congenic tenascin-C knockout mice, the dermatitis occurred more severely than in wild-type mice; infiltration of polymorphonuclear cells in knockout mice persisted longer than in wild-type mice, and the elastosis-like disorganized extracellular matrix was also seen in the ear. These results suggest that tenascin-C plays a role in vivo in inflammatory responses in the skin, and that the genetic background has profound effects on the function of tenascin-C in mouse dermatitis.
腱生蛋白-C是一种大型细胞外基质糖蛋白,其特点是在胚胎发育、致癌过程和伤口愈合期间具有时空表达。许多关于腱生蛋白-C的体外研究揭示了其多功能特性;然而,腱生蛋白-C基因的破坏在发育过程中并未显示出任何明显异常,其在体内的功能仍不清楚。在此,我们通过研究腱生蛋白-C基因敲除小鼠的化学诱导性皮炎,来调查腱生蛋白-C是否参与成人的炎症性皮炎。将半抗原2,4-二硝基氟苯经皮应用于BALB/CA小鼠的耳部皮肤会导致炎症,并诱导腱生蛋白-C的表达。在同基因腱生蛋白-C基因敲除小鼠中,皮炎比野生型小鼠更严重;基因敲除小鼠中多形核细胞的浸润持续时间比野生型小鼠更长,并且在耳部还可见到类似弹性组织变性的细胞外基质紊乱。这些结果表明,腱生蛋白-C在皮肤炎症反应中在体内发挥作用,并且遗传背景对腱生蛋白-C在小鼠皮炎中的功能有深远影响。