کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8715944 | 1587875 | 2018 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers
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کلمات کلیدی
DSBCFUqPCRMIRIPADFUFFPE - MEPQuantitative PCR - PCR کمیMRSA - استافیلوکوک اورئوس مقاوم به متی سیلین یا MRSA methicillin-resistant Staphylococcus aureus - استافیلوکوک اورئوس مقاوم به متیسیلینIngenuity Pathway Analysis - تجزیه و تحلیل راه IngenuityDiabetic foot ulcer - زخم پای دیابتیdouble-strand break - شکست دو ردیفformalin-fixed paraffin-embedded - فرمالین ثابت پارافین تعبیه شده استMicroRNA - میکرو RNA colony-forming unit - واحد تشکیل کلنی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers](/preview/png/8715944.png)
چکیده انگلیسی
Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes in which bacterial presence, including the frequent colonizer Staphylococcus aureus, contributes to inhibition of healing. MicroRNAs (miRs) play a role in healing and host response to bacterial pathogens. However, the mechanisms by which miR response to cutaneous S. aureus contributes to DFU pathophysiology are unknown. Here, we show that S. aureus inhibits wound closure and induces miR-15b-5p in acute human and porcine wound models and in chronic DFUs. Transcriptome analyses of DFU tissue showed induction of miR-15b-5p to be critical, regulating many cellular processes, including DNA repair and inflammatory response, by suppressing downstream targets IKBKB, WEE1, FGF2, RAD50, MSH2, and KIT. Using a human wound model, we confirmed that S. aureus-triggered miR-15b-5p induction results in suppression of the inflammatory- and DNA repair-related genes IKBKB and WEE1. Inhibition of DNA repair and accumulation of DNA breaks was functionally confirmed by the presence of the pH2AX within colonized DFUs. We conclude that S. aureus induces miR-15b-5p, subsequently repressing DNA repair and inflammatory response, showing a mechanism of inhibition of healing in DFUs previously unreported, to our knowledge. This underscores a previously unknown role of DNA damage repair in the pathophysiology of DFUs colonized with S. aureus.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 5, May 2018, Pages 1187-1196
Journal: Journal of Investigative Dermatology - Volume 138, Issue 5, May 2018, Pages 1187-1196
نویسندگان
Horacio A. Ramirez, Irena Pastar, Ivan Jozic, Olivera Stojadinovic, Rivka C. Stone, Nkemcho Ojeh, Joel Gil, Stephen C. Davis, Robert S. Kirsner, Marjana Tomic-Canic,