Pharmacological preconditioning of random-pattern skin flaps with local FK506 in nicotine-treated rats: interaction with nitric oxide system

Nezami, Behtash Ghazi; Rahimpour, Sina; Sianati, Setareh; Anaraki, Dina Kalbasi; Sadeghi, Mahsa; Ghasemi, Mehdi; Dehpour, Ahmad Reza

doi:10.1016/j.bjps.2008.11.083

Cited by 5 publications

(4 citation statements)

References 5 publications

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“…Selective targeting of FKBP12 protects from chronic injury in the heart and liver. Effectiveness of FK506 had been documented in various parenchymal organs (4)(5)(6)(7)(8)(9)(10)(11)(12), in line with transcriptional Arnt induction present in the kidney (confirming previous results) and also in the heart, brain, spinal cord, skin, liver, lung, and intestine in response to FK506 or GPI-1046 (0.2 mg/kg or 30 mg/kg orally per day, respectively; Figure 11, A and B). Based on robust Arnt induction observed in the heart and liver (Supplemental Figure 8, A and B), we next analyzed the presence of an Fkbp12/Yy1/Arnt/Alk3 signaling axis in rodent models of cardiac fibrosis after continuous minipump delivery of angiotensin II (AT II) and carbon tetrachloride-induced (CCl 4 -induced) liver failure (23,38).…”

Section: Resultssupporting

confidence: 83%

“…Among different preconditioning approaches, several independent studies highlighted efficacy of FK506 (synonym, tacrolimus or fujimycin) administration to protect against acute experimental injuries (4) involving various parenchymal organs, including kidney (5), heart (6), liver (7), lung (8), brain (9), spinal cord (10), skin (11), and intestine (12). FK506 is a macrolide calcineurin inhibitor (CNI) that elicits immunosuppression by forming a complex with distinct FK506-binding proteins (FKBPs) to attenuate transcription of proinflammatory cytokines dependent on nuclear factor of activated T cells (NFAT) and NF-κB (13).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological induction of hypoxia-inducible transcription factor ARNT attenuates chronic kidney failure

Tampe¹,

Tampe²,

Nyamsuren³

et al. 2018

Journal of Clinical Investigation

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Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge because, once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury. We identified a protective mechanism controlled by the transcription factor ARNT that effectively inhibits progression of chronic kidney injury by transcriptional induction of ALK3, the principal mediator of antifibrotic and proregenerative bone morphogenetic protein-signaling (BMP-signaling) responses. We further report that ARNT expression itself is controlled by the FKBP12/YY1 transcriptional repressor complex and that disruption of such FKBP12/YY1 complexes by picomolar FK506 at subimmunosuppressive doses increases ARNT expression, subsequently leading to homodimeric ARNT-induced ALK3 transcription. Direct targeting of FKBP12/YY1 with in vivo morpholino approaches or small molecule inhibitors, including GPI-1046, was equally effective for inducing ARNT expression, with subsequent activation of ALK3-dependent canonical BMP-signaling responses and attenuated chronic organ failure in models of chronic kidney disease, and also cardiac and liver injuries. In summary, we report an organ-protective mechanism that can be pharmacologically modulated by immunophilin ligands FK506 and GPI-1046 or therapeutically targeted by in vivo morpholino approaches.

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Section: Resultssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Pharmacological induction of hypoxia-inducible transcription factor ARNT attenuates chronic kidney failure

Tampe¹,

Tampe²,

Nyamsuren³

et al. 2018

Journal of Clinical Investigation

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“…Nezami et al . 25 demonstrated that single, local and low doses of tacrolimus reduced the area of skin flap necrosis in nicotine treated rats significantly, 28.3% in the treatment group and 53.9% in the control group by reducing the oxidative stress produced by nicotine.…”

Section: Discussionmentioning

confidence: 95%

Use of derived adipose stem cells to reduce complications of cutaneous scarring in smokers. An experimental model in rats

Martins

Oliveira

Lima³

et al. 2019

Acta Cir. Bras.

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Purpose To evaluate the use of adipose-derived stem cells (ADSC) in reducing the necrosis area in an experimental model of cutaneous ischemic flap in rats submitted to subcutaneous nicotine injection to simulate a smoker patient. Methods In an experimental study, 30 rats were enrolled and divided into two experimental groups of 15 animals all submitted to a subcutaneous nicotine injection to create ischemic cutaneous flaps on their backs. Other 10 animals were used only to obtain adipose tissue derived stem cells (ADSC). The first group (n=15) received ADSC treatment at the end of surgery while the other group, the control (n=15), received no other interventions. After euthanasia, a decal was performed on the whole area of the flap, accurately defining the transition from necrosis to healthy region. Photos of all animals were collected and evaluated by scales standardized by Paint-Autocad- 2015 software to define the area of flap necrosis in each rat. Student T test was performed to compare the groups, considering a p< 0.05 significant. Data were analyzed using SPSS IBM ® 18 version. Results Through the analysis of the images by the program Paint-Autocad-2015 and the area of decal obtained by the transparent sheet, we obtained a mean of 46% necrosis of the total area of the flap in the treatment group and 69.4% in the control group. In the descriptive analysis, a mean of 3.7 cm of necrosis CI 95% (3.2 - 4.2) was evident in the treatment group whereas a mean value of 5.56 CI 95% (5.2 - 5.9) was found in control group, with p value <0.001 for this comparison. Conclusion The application of adipose-derived stem cells reduces the percentage of necrosis in an experimental model of randomized cutaneous flap in rats submitted to subcutaneous nicotine injection.

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“…Among these agents are NO, opioids, ACE inhibitors, K ATP channel openers, and immunophilin ligands [13][14][15]17]. The final role of these agents is to enhance cellular energy consumption and to delay the apoptotic trigger in ischemic conditions.…”

Section: Discussionmentioning

confidence: 98%

Chronic Lithium Impairs Skin Tolerance to Ischemia in Random-Pattern Skin Flap of Rats

Nezami¹,

Rahimpour²,

Sadeghi³

et al. 2011

Journal of Surgical Research

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Pharmacological preconditioning of random-pattern skin flaps with local FK506 in nicotine-treated rats: interaction with nitric oxide system

Cited by 5 publications

References 5 publications

Pharmacological induction of hypoxia-inducible transcription factor ARNT attenuates chronic kidney failure

Pharmacological induction of hypoxia-inducible transcription factor ARNT attenuates chronic kidney failure

Use of derived adipose stem cells to reduce complications of cutaneous scarring in smokers. An experimental model in rats

Chronic Lithium Impairs Skin Tolerance to Ischemia in Random-Pattern Skin Flap of Rats

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