Epidermal regulation of dermal fibroblast activity
Epidermal regulation of dermal fibroblast activity
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DOI：
10.1097/00006534-199807000-00021
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发表时间：
1998-07-01
影响因子：
3.6
通讯作者：
Garner, WL
中科院分区：
文献类型：
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作者：
Garner, WL
虽然烧伤创面延迟愈合和随后的增生性瘢痕形成之间的联系是明确的，但这种关系的机制尚不清楚。未愈合的烧伤创面缺乏表皮，这表明表皮在控制真皮成纤维细胞基质合成中可能具有调节作用。因此，我们研究了表皮细胞和表皮细胞条件培养基对成纤维细胞胶原合成和复制的影响。纯化的成纤维细胞和角质形成细胞株从丢弃的正常成人皮肤中开发。通过将无精氨酸和无血清培养基与汇合的成纤维细胞或角质形成细胞培养物孵育18小时来产生条件培养基（n = 3）。将几乎汇合的成纤维细胞培养物暴露于分级浓度的非条件培养基（对照）、条件培养基或不同数量的角质形成细胞48小时。通过掺入H-3-胸苷定量复制。胶原合成通过将H-3-脯氨酸掺入胶原酶敏感蛋白中来测量。采用方差分析（ANOVA）和线性回归对数据进行比较。角质细胞条件培养基诱导复制的显著增加（n = 3）（p = 0.004）和胶原合成的减少（n = 6）（p < 0.001）。相比之下，成纤维细胞条件培养基和对照培养基对成纤维细胞复制或胶原合成都没有影响。成纤维细胞与分级数量的角质形成细胞的共培养类似地降低胶原蛋白合成（n = 6）（p < 0.001）。真皮成纤维细胞胶原合成似乎是由可溶性角质形成细胞产物调节的。这一结果提示了临床观察的一种机制，即缺乏表皮的未愈合烧伤伤口表现出过量的胶原蛋白产生和瘢痕。减少增生性瘢痕的临床策略应包括尝试用皮肤移植或应用培养的上皮自体移植物早期闭合伤口。
Although the association between delayed burn wound healing and subsequent hypertrophic scar formation is well-established, the mechanism for this relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a possible regulatory role for the epidermis in controlling dermal fibroblast matrix synthesis. Therefore, we examined the effect of epidermal cells and media conditioned by epidermal cells on fibroblast collagen synthesis and replication. Purified fibroblast and keratinocyte cell strains were developed from discarded normal adult human skin. Conditioned media were created by incubation of cytokine-free and serum-free medium with either confluent fibroblast or keratinocyte cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed for 48 hours to graded concentrations of either unconditioned medium (control), conditioned medium, or varying numbers of keratinocytes. Replication was quantified by the incorporation of H-3-thymidine. Collagen synthesis was measured by the incorporation of H-3-proline into collagenase-sensitive protein. Data were compared using analysis of variance (ANOVA) and linear regression. Keratinocyte conditioned medium induced a significant increase in replication (n = 3) (p = 0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast, neither fibroblast conditioned medium nor control medium had an effect on fibroblast replication or collagen synthesis. Co-culture of fibroblast with a graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p < 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a soluble keratinocyte product. This result suggests a mechanism for the clinical observation that unhealed burn wounds, which lack the epidermis, demonstrate excess collagen production and scar. Clinical strategies to decrease hypertrophic scar should include an attempt at early wound closure with skin grafting or the application of cultured epithelial autografts.