Effect of FK506 in reducing scar formation by inducing fibroblast apoptosis after sciatic nerve injury in rats.
Effect of FK506 in reducing scar formation by inducing fibroblast apoptosis after sciatic nerve injury in rats.
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FK506 通过诱导大鼠坐骨神经损伤后成纤维细胞凋亡减少疤痕形成的作用。
DOI：
10.1038/cddis.2013.56
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发表时间：
2013-03-07
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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作者：
FK506是一种广泛应用于器官移植的免疫抑制剂，可通过减少瘢痕形成促进周围神经再生。然而，人们对FK506如何减少瘢痕形成知之甚少。本实验研究了FK506对大鼠坐骨神经损伤后成纤维细胞增殖的影响及其与瘢痕形成的关系，并进一步探讨了FK506对成纤维细胞增殖和凋亡的影响。Masson染色和免疫组织化学结果显示，FK506治疗后坐骨神经损伤大鼠神经吻合口瘢痕面积和成纤维细胞数量明显减少。直线相关分析显示，瘢痕面积与成纤维细胞数量呈显著正相关。CCK-8比色法和流式细胞仪检测表明，FK506在体外也能抑制成纤维细胞的增殖并诱导其凋亡。在成纤维细胞的凋亡过程中，主要是JNK和ERK的磷酸化被激活。JNK抑制剂SP600125或ERK抑制剂PD98059可分别抑制FK506诱导的成纤维细胞凋亡。此外，同时应用这两种抑制剂在保护细胞免受凋亡方面具有相加的作用。这些结果提示，FK506诱导的成纤维细胞凋亡可能通过抑制成纤维细胞的增殖而减少坐骨神经损伤后瘢痕的形成，JNK和ERK参与了FK506诱导的成纤维细胞的凋亡。
We previously demonstrated that FK506, a generally applied immunosuppressant in organ transplantation, could promote peripheral nerve regeneration through reducing scar formation. However, little is known about how FK506 reduces scar formation. Herein we investigated the influence of FK506 on fibroblast proliferation and its correlation with scar formation after sciatic nerve injury in rats, and further explored the effect of FK506 on fibroblast proliferation and apoptosis in vitro. Masson staining and immunohistochemistry revealed that scar area and fibroblast number in the nerve anastomosis of sciatic nerve-injured rats were significantly reduced after FK506 administration. The scar area had a significant positive correlation with the fibroblast number, as detected by linear correlation analysis. CCK-8 assay and flow cytometry indicated that FK506 also inhibited proliferation and induced apoptosis of fibroblasts in vitro. It was primarily phosphorylation of JNK and ERK that were activated during the apoptosis of fibroblast. Pretreatment of cells with JNK inhibitor, SP600125, or ERK inhibitor, PD98059, could inhibit FK506-induced fibroblast apoptosis, respectively. Moreover, simultaneous application of both inhibitors had additive roles in cell protection from apoptosis. These results suggest that FK506-induced fibroblast apoptosis contributes to the suppression of fibroblast proliferation and then results in the reduction of scar formation in sciatic nerve-injured rat, and that JNK and ERK are involved in FK506-induced fibroblast apoptosis.
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影响因子：
6.1
作者：
Que J;Cao Q;Sui T;Du S;Zhang A;Kong D;Cao X
通讯作者：
Cao X
影响因子：
4.1
作者：
Dougherty, CJ;Kubasiak, LA;Webster, KA
通讯作者：
Webster, KA
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
DOI：
10.2106/00004623-196749040-00008
发表时间：
1967-01-01
影响因子：
5.3
作者：
BORA, FW
通讯作者：
BORA, FW
DOI：
10.1080/10731190802375810
发表时间：
2008-01-01
期刊：
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND BIOTECHNOLOGY
影响因子：
--
作者：
Han Haisheng;Zuo Songjie;Li Xin
通讯作者：
Li Xin