title: Delayed wound healing and dysregulation of IL6/STAT3 signalling in MSCs derived from pre-diabetic obese mice.
abstract: 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.
authors: Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. Electronic address: vandevyverm@sun.ac.za.
authors: M
authors: M
authors: van de Vyver
authors: Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Private Bag X01, Scottsville, 3209, South Africa. Electronic address: Niesler@ukzn.ac.za.
authors: C
authors: C
authors: Niesler
authors: Department of Physiological Sciences, Stellenbosch University, South Africa. Electronic address: khm@sun.ac.za.
authors: K H
authors: KH
authors: Myburgh
authors: Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. Electronic address: wferris@sun.ac.za.
authors: W F
authors: WF
authors: Ferris
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D015870:Gene Expression; D015850:Interleukin-6 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D011236:Prediabetic State / Q000378:metabolism / Q000503:physiopathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: Diabetes; Interleukin-6; Mesenchymal stem cells; Obesity; STAT3