Xie Feng, Chai Jiake, Zhang Zhengwen, Hu Quan, Ma Tengxiao
Department of Plastic Surgery, Henan Province People's Hospital, Zhengzhou, China.
Department of Burn, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
Transpl Int. 2015 Oct;28(10):1143-51. doi: 10.1111/tri.12590.
MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis, and metastasis. However, the role of Mir-26a in transplant rejection has never been investigated. Full-thickness skin grafts 1-2 cm in diameter were obtained from the tail-skin CBA/J donor mice and transplanted onto the back of wild-type C57Bl/6 recipient mice. Vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 × 10(7) transforming units of recombinant lentivirus were injected to mice once through the tail vein. Mir-26a overexpression results in prolonged skin allograft survival (MST = 9.5 days in LV-Con mice; MST = 22 days in LV-26a mice. P < 0.01) and promoted regulatory T cells (Tregs) expansion. The prolonged skin allograft survival induced by LV-26a was abrogated by depletion of Tregs with anti-CD25 antibodies. Mir-26a significantly promoted IL-10 expression and suppressed the expression of IL-6, IL-17, and IFN-γ. Furthermore, IL-6 overexpression led to complete suppression of the Mir-26a-induced upregulation of Foxp3. The prolonged allograft survival induced by LV-Mir-26a was also completely abrogated by IL-6 overexpression. In conclusion, Mir-26a prolongs skin allograft survival and promotes Tregs expansion in part through inhibition of IL-6 expression.
据报道，微小RNA 26a（Mir-26a）在细胞分化、细胞生长、细胞凋亡和转移中发挥作用。然而，Mir-26a在移植排斥反应中的作用从未被研究过。从尾皮CBA/J供体小鼠获取直径1-2厘米的全层皮肤移植物，并移植到野生型C57Bl/6受体小鼠的背部。通过尾静脉向小鼠一次性注射编码前体Mir-26a的载体（LV-26a）和空的慢病毒载体（LV-Con），二者均携带约2×10⁷个重组慢病毒转化单位。Mir-26a过表达导致皮肤同种异体移植物存活时间延长（LV-Con小鼠的平均存活时间 = 9.5天；LV-26a小鼠的平均存活时间 = 22天。P < 0.01），并促进调节性T细胞（Tregs）扩增。用抗CD25抗体清除Tregs可消除LV-26a诱导的皮肤同种异体移植物存活时间延长。Mir-26a显著促进IL-10表达，并抑制IL-6、IL-17和IFN-γ的表达。此外，IL-6过表达导致Mir-26a诱导的Foxp3上调完全受到抑制。LV-Mir-26a诱导的移植物存活时间延长也因IL-6过表达而完全消除。总之，Mir-26a通过部分抑制IL-6表达来延长皮肤同种异体移植物存活时间并促进Tregs扩增。
