Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate.

Autor: Botusan IR; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.; Department of Endocrinology, Diabetes and Metabolism, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; Center for Diabetes, Academic Specialist Center, Stockholm County Council, Sweden., Zheng X; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.; Department of Endocrinology, Diabetes and Metabolism, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Narayanan S; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden., Grünler J; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden., Sunkari VG; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden., Calissendorff FS; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden., Ansurudeen I; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden., Illies C; Department of Clinical Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Svensson J; Institute of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden., Jansson JO; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden., Ohlsson C; Institute of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden., Brismar K; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.; Department of Endocrinology, Diabetes and Metabolism, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Catrina SB; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.; Department of Endocrinology, Diabetes and Metabolism, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; Center for Diabetes, Academic Specialist Center, Stockholm County Council, Sweden.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Mar 13; Vol. 13 (3), pp. e0193084. Date of Electronic Publication: 2018 Mar 13 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0193084
Abstrakt: 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.
Databáze: MEDLINE
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