肝源性胰岛素样生长因子-I（IGF-I）缺乏并不影响皮肤伤口愈合速度。
Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate.
机构信息
Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.
Department of Endocrinology, Diabetes and Metabolism, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
出版信息
PLoS One. 2018 Mar 13;13(3):e0193084. doi: 10.1371/journal.pone.0193084. eCollection 2018.
OBJECTIVE
IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes).
METHODS
LI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry.
RESULTS
The wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding.
CONCLUSION
Deficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normoglycemic conditions nor in diabetes.
目的
IGF-I 是一种生长因子，几乎存在于所有组织中。然而，循环中的 IGF-I 主要来源于肝脏。IGF-I 促进伤口愈合，其水平在再生潜能低的伤口（如糖尿病伤口）中降低。然而，循环 IGF-I 对伤口愈合的贡献尚不清楚。在这里，我们研究了在正常（血糖正常）和受损的伤口愈合（糖尿病）期间，肝脏源性 IGF-I 缺乏（LI-IGF-I-/- 小鼠）的小鼠中，全身性 IGF-I 对伤口愈合速度的作用。
方法
使用 Cre/loxP 重组系统生成肝细胞中 IGF-I 基因完全失活的 LI-IGF-I-/- 小鼠，导致循环 IGF-I 减少 75%。链脲佐菌素诱导 LI-IGF-I-/- 和对照小鼠发生糖尿病。在小鼠背部制作伤口，评估伤口愈合率和组织学。用 RIA 和 ELISA 分别测量血清 IGF-I 和 GH。用 qRT-PCR 评估皮肤中 IGF-I、IGF-II 和 IGF-I 受体的表达。通过免疫组织化学分析伤口愈合过程中不同细胞类型中局部 IGF-I 蛋白的表达。
结果
LI-IGF-I-/- 小鼠的伤口愈合率与对照组相似。糖尿病显著延迟了 LI-IGF-I-/- 和对照组小鼠的伤口愈合率。然而，在具有正常或减少的肝 IGF-I 产生的糖尿病动物之间，没有观察到显著差异。在任何一组测试的动物中，皮肤中 IGF-I、IGF-II 和 IGF-I 受体的基因表达均无差异。尽管在 LI-IGF-I-/- 小鼠的伤口中观察到白细胞中 IGF-I 表达的短暂减少，但 LI-IGF-I-/- 和 WT 小鼠伤口中的局部 IGF-I 水平相似。
结论
肝源性 IGF-I 的缺乏不影响小鼠的伤口愈合，无论是在血糖正常的情况下还是在糖尿病中。
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