Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts
Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts
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DOI：
10.14670/hh-27.515
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发表时间：
2012-04-01
影响因子：
2
通讯作者：
Yamate, Jyoji
中科院分区：
文献类型：
--
作者：
Juniantito, Vetnizah;Izawa, Takeshi;Yamate, Jyoji
创伤后的皮肤纤维化是由能够产生胶原的肌成纤维细胞引起的；其来源和特征仍有待研究。对大鼠创面切除后1~26天的肌成纤维细胞的免疫表型特征进行了分析。肌成纤维细胞表达中间细胞骨架，如波形蛋白、结蛋白和α-平滑肌肌动蛋白(α-SMA)。为了寻找祖细胞，使用基质/骨髓干细胞标记物(Thy-1和A3)进行了免疫标记分析。肌成纤维细胞对波形蛋白和α-SMA的反应始于妊娠第5天，在妊娠第9天肉芽组织中达到高峰，在重塑组织中逐渐减少，这些免疫阳性细胞与Thy-1同时反应。结蛋白反应细胞仅局限于创面床内新生血管。单/双标记法显示，新生血管周细胞对波形蛋白、α-SMA、Thy-1、A3呈阳性反应，对内皮标志物呈阴性反应，偶见结蛋白；创面周围小叶周围真皮鞘细胞中，波形蛋白、Thy-1、A3表达增强。新生血管中的肌成纤维细胞(表达波形蛋白、α-SMA和Thy-1)、周细胞(对波形蛋白、α-SMA、Thy-1和A3有反应)和小叶周围真皮鞘细胞(对波形蛋白、Thy-1和A3有反应)具有相当大的免疫表型相似性。总的来说，大鼠皮肤纤维化中的肌成纤维细胞以波形蛋白、α-SMA和Thy-1的表达为特征，这些细胞可能是由基质/骨髓干细胞谱系中的周细胞或小叶周围真皮鞘细胞产生的。
Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing collagen; the derivation and features remain to be investigated. Immunophenotypical characteristics of myofibroblasts were analysed in excisional rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to 26. Myofibroblasts were characterized for expressions of intermediate cytoskeletons such as vimentin, desmin, and alpha-smooth muscle actin (alpha-SMA). To pursue the progenitor, immunolabeling analyses were performed using stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to vimentin and alpha-SMA were first seen on PW day 5, then peaked on PW day 9 in granulation tissues, and gradually decreased in remodeling tissues; these immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were limited to newly-formed blood vessels in wound bed. The single/double immunolabelings revealed that pericytes (identified by positive reaction to PDGFR-beta and negative reaction to endothelial markers) in newly-developing blood vessels reacted to vimentin, alpha-SMA, Thy-1 and A3, and occasionally to desmin, and that perifollicular dermal sheath cells in the wound periphery showed increased expressions for vimentin, Thy-1 and A3. There is considerable immunophenotypical similarity between myofibroblasts (expressing vimentin, alpha-SMA and Thy-1), pericytes (reacting to vimentin, alpha-SMA, Thy-1 and A3) in newly-developing blood vessels, and perifollicular dermal sheath cells (reacting to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous fibrosis are characterized by vimentin, alpha-SMA and Thy-1 expressions, and the cells might be generated from the pericytes or perifollicular dermal sheath cells in the lineage of stroma-/bone marrow-stem cells.