Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Expression of miR-146a and miR-378a in wound fluid: A possible biomarker for poor wound healing in diabetes   (#43)

Carla Cannizzo 1 , Luisa Olaya Agudo 1 , Maryam Abdollahi 1 , Taria Ng 1 , Surya Sutanto 1 , Susan McLennan 1 2 3
  1. Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School, Charles Perkins Centre, Bosch Institute, University of Sydney, Camperdown, NSW, Australia
  2. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. NSW Health Pathology, Sydney, NSW, Australia

Increasing evidence suggests that micro-RNAs (miRs) may serve as potential biomarkers of healing. miR-146a and miR-378a are involved in inflammation and fibroblast migration respectively and are thus associated with poor wound closure. Whether these miRs are detectable in wound fluid (WF) and are altered in diabetes has not been investigated.

Male Sprague-Dawley rats were injected intraperitoneally with streptozotocin (STZ:65mg/kg) to induce diabetes (D: n=11) and were maintained for 6 weeks with Insulin (2-6U Humalog® 25). After 6wks diabetic and age-matched non-diabetic rats (C: n=8) were anesthetized and 4x1cm2 PVC sponges were implanted subcutaneously.  On day 6 post-surgery, animals were euthanized and plasma (P) as well as WF from harvested sponges were obtained. miRs were extracted  (P:400µl and WF:200µl) and their expression measured by  qRT-PCR using Taqman probes.  Results were normalized to exogenous Caenorhabditis elegans miR-39 and reported as mean ±SD.

Diabetic animals had significantly higher blood glucose levels and lower body weight compared to controls (each P<0.05). In controls there was an increase in WF miR-146a (P:64.53 ± 38.91 vs WF:3131±1598, P<0.001) and miR-378a (P:2.603± 1.891vs WF:46.21±50.02, P<0.001) when compared to plasma, this pattern was also seen in diabetic animals:  miR-146a (P:88.53 ± 55.92 vs WF:21728±25762, P<0.0001) and miR-378a (P:7.398± 2.608 vs WF:27.86±6.403, P<0.005).  In addition miR-146a was significantly increased in the WF of diabetic rats when compared to control (C:3131± 1598 vs D:21728±25762, P<0.05). This increase was not seen in the plasma.

These results indicate for the first time that miR-146a and miR-378a are present in WF in this model. The increase in miR-146a in diabetic WF suggests its utility as a potential biomarker for poor wound healing. Whether these changes are observed in human WFs and their levels are altered in association with wound healing rate remains to be investigated.