Effect of Rapamycin on Wound Healing: An Experimental Study

Ekici, Yahya; Emiroğlu, R; Özdemir, Hamiyet Hekimci; Aldemir, D.; Karakayalı, H.; Haberal, Mehmet

doi:10.1016/j.transproceed.2007.04.013

Cited by 37 publications

(25 citation statements)

References 8 publications

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“…However, the high wound healing complication rates after kidney transplantation (49) and tracheal anastomosis complication after lung transplantation (50) may limit the clinical application of rapamycin immediately after transplantation. Animal studies have shown that rapamycin impairs all steps of the wound healing process (51). Better strategies targeting PTEN/AKT are needed to reduce the oncogenic effect of CsA.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive Cyclosporin A Activates AKT in Keratinocytes through PTEN Suppression

Han¹,

Ming²,

et al. 2010

Journal of Biological Chemistry

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Non-melanoma skin cancer, the most common neoplasia after solid organ transplantation, causes serious morbidity and mortality and is related to sun exposure. Cyclosporin A (CsA) has been used widely to prevent rejection in organ transplantation. The mechanism of CsA action in causing cancer was thought to be well understood via immunosuppression. Here, we show that CsA promotes primary skin tumor growth in immune-deficient mice and keratinocyte growth in vitro. In addition, CsA enhances keratinocyte survival from removal of extracellular matrix or UVB radiation. At the molecular level, CsA increases AKT activation after serum treatment and UVB irradiation. Furthermore we found that expression of PTEN, the negative regulator of AKT activation, is significantly reduced post-CsA in human HaCaT and A431 cells and in mouse skin in vivo. CsA-induced PTEN down-regulation occurs at the transcription level and is epidermal growth factor receptor-dependent. Such PTEN suppression is required for increased AKT activation. Inhibition of AKT activation abolishes CsA-promoted growth and survival, indicating that AKT hyperactivation is essential for both growth and survival of CsA-treated cells. In addition, mTOR signaling as a known AKT downstream pathway is required for CsA-enhanced growth and survival. Taken together, we have identified the PTEN/AKT pathway as new molecular targets of CsA in epidermal keratinocytes, suggesting a previously unknown mechanism in CsA-enhanced skin carcinogenesis. Our findings challenge assumptions about how CsA-associated tumors arise in skin.

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Section: Discussionmentioning

confidence: 99%

Immunosuppressive Cyclosporin A Activates AKT in Keratinocytes through PTEN Suppression

Han¹,

Ming²,

et al. 2010

Journal of Biological Chemistry

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“…The effect on the development of wound strength becomes apparent after the third post-operative day and persists for at least four weeks after surgery in experimental anastomoses [16,18]. Several mechanisms of action have been proposed to explain the negative effects of everolimus on wound healing, including deposition of insufficient collagen, a prolonged proliferation phase, disruption of the remodeling phase, and reduced inflammatory cell infiltration [18,26].…”

Section: Discussionmentioning

confidence: 99%

Extending Myringotomy Patency with Topical Everolimus in Rats

et al. 2016

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“…Furthermore, Schaffer et al (19) studied the effects of tacrolimus in the healing of intestinal tissue and dermis and observed that the administration of 2mg/kg of tacrolimus led to a reduction in the healing dermis of animals. On the other hand, regarding the study of urothelial tissue, Ekici et al (20) looked at the effects of immunosuppression with sirolimus in the healing of sutures in the bladder of rats and concluded that sirolimus affects all stages of healing of the bladder, including reducing the number of inflammatory cells, angiogenesis and the proliferation of myofibroblasts, thus delaying the healing process.…”

Section: Discussionmentioning

confidence: 99%

Qualitative analysis of the deposit of collagen in bladder suture of rats treated with tacrolimus combined with mycophenolate-mofetil

2014

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ARTICLE INFO ______________________________________________________________ ______________________Purpose: To evaluate the synthesis of type I (mature) and type III (immature) collagen in bladder suture of rats treated with a combination of tacrolimus and mycophenolate mofetil for 15 days. Materials and Methods:Thirty rats were divided into 3 groups: the sham, control and experimental groups. All the animals underwent laparotomy, cystotomy and bladder suture in two planes with surgical PDS 5-0 thread. The sham group did not receive treatment. The control group received saline solution, and the experimental group received 0.1mg/kg/day of tacrolimus with 20mg/kg/day of mycophenolate mofetil, for 15 days. From then on, the tacrolimus was dosed. The surgical specimens of the bladder suture area were processed so that the total type I and type III collagen could be measured by the picrosirius red technique.Results: There was a predominance of type I collagen production in the sham and control groups compared to the experimental group, in which type III collagen was predominant. The production of total collagen did not change. Conclusion:The association of tacrolimus and mycophenolate mofetil in animals qualitatively changes the production of collagen after 15 days with a predominance of type III collagen.

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Effect of Rapamycin on Wound Healing: An Experimental Study

Cited by 37 publications

References 8 publications

Immunosuppressive Cyclosporin A Activates AKT in Keratinocytes through PTEN Suppression

Immunosuppressive Cyclosporin A Activates AKT in Keratinocytes through PTEN Suppression

Extending Myringotomy Patency with Topical Everolimus in Rats

Qualitative analysis of the deposit of collagen in bladder suture of rats treated with tacrolimus combined with mycophenolate-mofetil

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