Inhibition of PAI-1 Via PAI-039 improves dermal wound closure in diabetes

18Citations
Citations of this article
33Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Diabetes impairs the ability to heal cutaneous wounds, leading to hospitalization, amputations, and death. Patients with diabetes experience elevated levels of plasminogen activator inhibitor 1 (PAI-1), regardless of their glycemic control. It has been demonstrated that PAI-1-deficient mice exhibit improved cutaneous wound healing, and that PAI-1 inhibition improves skeletal muscle repair in mice with type 1 diabetes mellitus, leading us to hypothesize that pharmacologically mediated reductions in PAI-1 using PAI-039 would normalize cutaneous wound healing in streptozotocin (STZ)-induced diabetic (STZ-diabetic) mice. To simulate the human condition of variations in wound care, wounds were aggravated or minimally handled postinjury. Following cutaneous injury, PAI-039 was orally administered twice daily for 10 days. Compared with nondiabetic mice, wounds in STZdiabetic mice healed more slowly. Wound site aggravation exacerbated this deficit. PAI-1 inhibition had no effect on dermal collagen levels or wound bed size. PAI- 039 treatment failed to improve angiogenesis in the wounds of STZ-diabetic mice and blunted angiogenesis in the wounds of nondiabetic mice. Importantly, PAI-039 treatment significantly improved epidermal cellular migration and wound re-epithelialization compared with vehicle-treated STZ-diabetic mice. These findings support the use of PAI-039 as a novel therapeutic agent to improve diabetic wound closure and demonstrate the primary mechanism of its action to be related to epidermal closure.

References Powered by Scopus

Global estimates of the prevalence of diabetes for 2010 and 2030

5547Citations
N/AReaders
Get full text

Cutaneous wound healing

5109Citations
N/AReaders
Get full text

National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants

2915Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Nrf2-Mediated Fibroblast Reprogramming Drives Cellular Senescence by Targeting the Matrisome

138Citations
N/AReaders
Get full text

A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice

58Citations
N/AReaders
Get full text

The interplay between hemostasis and immune response in biomaterial development for osteogenesis

51Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Rebalka, I. A., Raleigh, M. J., D’Souza, D. M., Coleman, S. K., Rebalka, A. N., & Hawke, T. J. (2015). Inhibition of PAI-1 Via PAI-039 improves dermal wound closure in diabetes. Diabetes, 64(7), 2593–2602. https://doi.org/10.2337/db14-1174

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 12

55%

Researcher 8

36%

Professor / Associate Prof. 1

5%

Lecturer / Post doc 1

5%

Readers' Discipline

Tooltip

Medicine and Dentistry 13

54%

Agricultural and Biological Sciences 7

29%

Engineering 3

13%

Chemistry 1

4%

Save time finding and organizing research with Mendeley

Sign up for free