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Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate
被引:18
作者:
Botusan, Ileana Ruxandra
[1
,2
,3
]
Zheng, Xiaowei
[1
,2
]
Narayanan, Sampath
[1
]
Grunler, Jacob
[1
]
Sunkari, Vivekananda Gupta
[1
]
Calissendorff, Freja S.
[1
]
Ansurudeen, Ishrath
[1
]
Illies, Christopher
[4
]
Svensson, Johan
[5
]
Jansson, John-Olov
[6
]
Ohlsson, Claes
[5
]
Brismar, Kerstin
[1
,2
]
Catrina, Sergiu-Bogdan
[1
,2
,3
]
机构:
[1] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden
[2] Karolinska Univ Hosp, Karolinska Inst, Dept Endocrinol Diabet & Metab, Stockholm, Sweden
[3] Stockholm Cty Council, Acad Specialist Ctr, Ctr Diabet, Stockholm, Sweden
[4] Karolinska Univ Hosp, Karolinska Inst, Dept Clin Pathol, Stockholm, Sweden
[5] Univ Gothenburg, Sahlgrenska Acad, Inst Internal Med, Gothenburg, Sweden
[6] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
来源:
基金:
瑞典研究理事会;
关键词:
TISSUE CONCENTRATIONS;
DIABETIC-PATIENTS;
HORMONE;
SYSTEM;
GENE;
MICE;
ABNORMALITIES;
MOUSE;
ACID;
D O I:
10.1371/journal.pone.0193084
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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.
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页数:11
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