Insulin-Like Growth Factor-1 Promotes Wound Healing in Estrogen-Deprived Mice: New Insights into Cutaneous IGF-1R/ERα Cross Talk

Emmerson, Elaine; Campbell, Laura; Davies, Faith C.J.; Ross, Nina L; Ashcroft, Gillian S.; Krust, Andrée; Chambon, Pierre; Hardman, Matthew J.

doi:10.1038/jid.2012.228

Cited by 77 publications

(57 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By not being alt ered during delayed wound closure in diabetic rats, they are presumably preventing the timely closure of wounds. Igf1 is induced in wounds, both in animals (57,58) and humans (59,60), but is missing in chronic wounds (61). Pro liferation and migration of keratinocytes and fibroblasts is promoted by Igf1 in vitro (62,63) and, interestingly, its levels are reduced in cells isolated from diabetic foot ulcers (64) and in diabetic mouse wounds (65).…”

Section: Resultsmentioning

confidence: 99%

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Bhattacharya

Aggarwal

Singh

et al. 2015

Mol Med

View full text Add to dashboard Cite

Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing.

show abstract

Section: Resultsmentioning

confidence: 99%

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Bhattacharya

Aggarwal

Singh

et al. 2015

Mol Med

View full text Add to dashboard Cite

show abstract

“…2) (27), adiponectin and IGF-I are likely to exert stronger effects on the overall equilibrium. Other reported benefits of IGF-I include repair of damaged tissue, inhibition of apoptosis, improved wound healing, angiogenesis, and cell proliferation (4,12,21,30,32,39,66,70,75), all of which are important in the regeneration of healthy adipose tissue in T1D.…”

Section: Discussionmentioning

confidence: 99%

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Gunawardana

Piston

2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Gunawardana SC, Piston DW. Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant. Am J Physiol Endocrinol Metab 308: E1043-E1055, 2015. First published April 21, 2015; doi:10.1152/ajpendo.00570.2014.-Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In nonobese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and longlasting euglycemia. In addition, BAT transplants placed prior to the onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulinlike growth factor-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants and implicate IGF-I as a likely mediator in the resulting equilibrium. type 1 diabetes; brown adipose tissue; insulin independent; transplantation; insulin-like growth factor I TYPE 1 DIABETES (T1D) is characterized by autoimmune-mediated destruction of pancreatic ␤-cells, resulting in absolute deficiency of insulin and loss of glycemic control. Treatments for T1D, despite having been refined over many years, are geared mainly toward replacing insulin, which involves numerous risks and limitations. Direct insulin replacement via daily injections or insulin pump does not cure the disease and requires life-long repeated administration. In addition to the inconvenience, direct insulin therapy requires careful monitoring of dosage and blood glucose levels and can lead to potentially fatal hypoglycemic episodes. Pancreas transplantation, the only available treatment with a good chance of long-term insulin independence, requires invasive surgery and life-long immunosuppressive therapy. Islet transplantation, although less invasive, is limited by the availability of donor tissue and the need for immunosuppression, and patients often return to insulin dependence in the long...

show abstract

“…[4] Growth factor therapies to induce angiogenesis and thereby enhance blood perfusion hold tremendous potential to address the shortcomings of current diabetic wound care modalities. [5,6] Among growth factor families, one of the most important proangiogenic mediators is the set of vascular endothelial growth factor (VEGF). Sufficient VEGF levels are believed to be essential for wound healing.…”

Section: Introductionmentioning

confidence: 99%

Combined effects of PLGA and vascular endothelial growth factor promote the healing of non-diabetic and diabetic wounds

Chereddy

Lopes

Koussoroplis

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

119

View full text Add to dashboard Cite

Insulin-Like Growth Factor-1 Promotes Wound Healing in Estrogen-Deprived Mice: New Insights into Cutaneous IGF-1R/ERα Cross Talk

Cited by 77 publications

References 76 publications

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Combined effects of PLGA and vascular endothelial growth factor promote the healing of non-diabetic and diabetic wounds

Contact Info

Product

Resources

About