EFFECT OF TGF-BETA-1 ON REEPITHILIALIZATION OF HUMAN KERATINOCYTES IN-VITRO - AN ORGANOTYPIC MODEL
EFFECT OF TGF-BETA-1 ON REEPITHILIALIZATION OF HUMAN KERATINOCYTES IN-VITRO - AN ORGANOTYPIC MODEL
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DOI：
10.1111/1523-1747.ep12396847
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发表时间：
1994-10-01
影响因子：
6.5
通讯作者：
TAICHMAN, LB
中科院分区：
文献类型：
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作者：
GARLICK, JA;TAICHMAN, LB
转化生长因子β -1 （tgf - β 1）已被证明在体外抑制角质细胞增殖，但在体内刺激伤口愈合。为了探索这一明显的悖论，我们研究了tgf - β 1对切口损伤后器官型培养细胞增殖和迁移的影响。器官型培养提供了一种更类似于活体的表皮组织，因此可能以不同于以前表皮分化不完全的培养模式的方式作出反应。在没有tgf - β 1的情况下，角化细胞对损伤的反应是过度增殖的。在2.5 ng/ml或更高的剂量下，在损伤后24小时观察到再上皮化的延迟以及过度增生的减少。然而，在48小时内，tgf - β 1处理的所有培养物都完成了再上皮化。特别是，7 ng/ml的tgf - β 1抑制增殖，但在48小时内对再上皮化没有影响。这些研究表明，1)tgf - β 1诱导了再上皮化的延迟，2)2.5 ng/ml剂量的tgf - β 1未抑制受伤角化细胞的增殖，以及3)7 ng/ml的tgf - β 1，在48小时内完成了再上皮化，尽管细胞增殖受到严重抑制。在器官型模型中，tgf - β 1似乎改变了再上皮化。
Transforming growth factor beta-1 (TGF-beta 1) has been shown to inhibit keratinocyte proliferation in vitro yet to stimulate wound healing in vivo. To explore this apparent paradox, the effect of TGF-beta 1 on proliferation and migration was investigated in organotypic cultures after incisional wounding. Organotypic cultures provide a more in vivo - like epidermal tissue and may therefore respond in a different manner than previous culture models in which epidermal differentiation is incomplete.Without TGF-beta 1, keratinocytes were hyperproliferative in response to wounding. At doses of 2.5 ng/ml or greater, a delay in re-epithelialization was seen at 24 h post-wounding along with a reduction in hyperproliferation. By 48 h, however, re-epithelialization was complete in all cultures treated with TGF-beta 1. In particular, 7 ng/ml TGF-beta 1 inhibited proliferation yet had no effect on re-epithelialization by 48 h. These studies demonstrate that i) TGF-beta 1 induced a delay in re-epithelialization, ii) proliferation of wounded keratinocytes was not inhibited at 2.5 ng/ml doses of TGF-beta 1, and iii) at 7 ng/ml TGF-beta 1, re-epithelialization was complete by 48 h in spite of the profound inhibition of cell proliferation. In the organotypic model, TGF-beta 1 appears to alter re-epithelialization.