Role of neutrophil associated lipocalin (NGAL) in poor wound healing in diabetes

Summary

Neutrophil gelatinase associated lipocalin plays a role in mediation of host defense against microorganisms. How it is regulated and whether its expression is altered in poorly healing wounds such as those which occur in diabetes is unknown and will be studied as part of this project.

Supervisor(s)

Dr Susan McLennan

Research Location

Camperdown - School of Medical Sciences - Bosch Institute

Program Type

Masters/PHD

Synopsis

Amongst the many chronic complications, diabetes causes impaired wound healing, and with it, increased morbidity. Up to 15% of all patients with diabetes will develop a foot ulcer and each year, in Australia, approximately 3000 diabetic patients require amputation secondary to foot ulceration. Despite concerted treatment, for reasons not completely understood many ulcers do not heal. Consequently, a detailed understanding of the wound healing process in diabetes and how it can be improved is of great importance. Our recent studies have shown that increased bacterial load and increased expression and activity of the one of the neutrophil gelatinases MMP-9 are associated with poor wound healing in diabetes. Neutrophil gelatinase associated lipocalin (NGAL), is secreted by neutrophils and in addition to bacteriostatic activity can to bind MMP-9. Whether NGAL expression is altered in wounds in diabetes and whether it correlates with poor wound healing is not known and will be studied as part of this project. In addition it is well recognized that the neutrophil changes its profile of actively transcribed genes when it diapedeses into wounded skin. This results in generation of signaling molecules, some of which support the growth and antimicrobial potential of keratinocytes and epithelial cells. Whether these are altered by high glucose or diabetes will also be investigated.

Additional Information

Investigation may include in vivo and in vitro studies in animal models of diabetes and in samples obtained from diabetic patients. Molecular tools such as techniques to knockdown (siRNA) and increase protein expression (AAV) are already available. Endpoints may include measurement of gene expression by real time RT-PCR, and protein by FACS, western blot or immunohistochemical techniques. 

Keywords

diabetes, diabetic complications, Nephropathy, fibrosis. inflammation, wound healing., Infectious diseases, Liver & hormonal disorders, Organ replacement, Pain & Trauma, Cell biology, Human body, Infection & immunity

Opportunity ID

The opportunity ID for this research opportunity is: 231

Other opportunities with Dr Susan McLennan

• Mechanism of the effect of diabetes on the inflammation and subsequent fibrosis
• Molecular studies of thyroid cancer and cutaneous squamous cell carcinoma