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
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.
引用
收藏
页数:11
相关论文
共 24 条
[21]   The hormonal action of IGF1 in postnatal mouse growth [J].
Stratikopoulos, Elias ;
Szabolcs, Matthias ;
Dragatsis, Ioannis ;
Klinakis, Apostolos ;
Efstratiadis, Argiris .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (49) :19378-19383
[22]   Selective blockade of estrogen receptor beta improves wound healing in diabetes [J].
Sunkari, Vivekananda Gupta ;
Botusan, Ileana R. ;
Savu, Octavian ;
Grunler, Jacob ;
Zheng, Xiaowei ;
Gustafsson, Jan-Ake ;
Brismar, Kerstin ;
Catrina, Sergiu-Bogdan .
ENDOCRINE, 2014, 46 (02) :347-350
[23]   Insulin-like growth factor I: a predictor of long-term glucose abnormalities in patients with acute myocardial infarction [J].
Wallander, M. ;
Brismar, K. ;
Ohrvik, J. ;
Ryden, L. ;
Norhammar, A. .
DIABETOLOGIA, 2006, 49 (10) :2247-2255
[24]   Normal growth and development in the absence of hepatic insulin-like growth factor I [J].
Yakar, S ;
Liu, JL ;
Stannard, B ;
Butler, A ;
Accili, D ;
Sauer, B ;
LeRoith, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7324-7329