Delayed wound healing and dysregulation of IL6/STAT3 signalling in MSCs derived from pre-diabetic obese mice

被引：25
作者：
van de Vyver, M. [1 ]
Niesler, C. [2 ]
Myburgh, K. H. [3 ]
Ferris, W. F. [1 ]
机构：
[1] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Med, Div Endocrinol, POB 241, ZA-8000 Cape Town, South Africa
[2] Univ KwaZulu Natal, Sch Life Sci, Discipline Biochem, Private Bag X01, ZA-3209 Scottsville, South Africa
[3] Univ Stellenbosch, Dept Physiol Sci, ZA-8000 Cape Town, South Africa
来源：
MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2016年 / 426卷 / 0C期
基金：
英国医学研究理事会;
关键词：
Interleukin-6; Mesenchymal stem cells; Diabetes; Obesity; STAT3; MESENCHYMAL STEM-CELLS; PROLIFERATION; PIOGLITAZONE; INFLAMMATION; MURINE; STAT3; INTERLEUKIN-6; REGENERATION; ACTIVATION; CHALLENGES;
D O I：
10.1016/j.mce.2016.02.003
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Metabolic dysfunction that occurs in obesity and Type 2 diabetes results in a low-level inflammatory state which impacts on mesenchymal stem cells (MSCs) capacity to promote wound healing. The ability of either recombinant Interleukin-6 (rIL6) or pioglitazone to modulate MSC migration, essential for wound healing, by targeting the inflammation-modulated IL6/STAT3 signalling pathway was therefore investigated in bone marrow-derived MSCs from control (C57BL/6J) and pre-diabetic obese mice (B6. Cg-Lepob/J). The population doubling time, in vitro wound closure and mRNA expression profile of 84 genes involved in the IL6/STAT3 signalling pathway were assessed. IL6/STAT3 signalling dysregulation, caused by IL6 deficiency, resulted in skewing of the immune modulatory properties of MSCs to favour a pro inflammatory profile. This could be nullified by addition of either rIL6 or conventional diabetes treatment. Therapies to improve diabetic wound healing should therefore focus on the cellular changes induced by the pathological inflammatory micro-environment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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页码：1 / 10
页数：10
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