High glucose activates ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic foot ulcers.

Abstract

Increased matrix metalloproteinase 9 (MMP9) expression is involved in delayed wound healing in diabetic foot ulcers. We created skin wounds in normal SD rats and STZ-induced diabetic SD rats, then we found protein levels of activator protein-1 (AP1), a crucial transcription factor to increase MMP9 transcription, as well as MMP9 was up-regulated in epithelium of diabetic skin tissues. Then, we evaluated the mRNA and protein stability of AP1 subunits C-FOS/C-Jun in HaCaT cells after high glucose treatment. Results showed that high glucose could increase protein stability of C-FOS and C-Jun. Additionally, high glucose also activated extracellular signaling-related kinase 1/2 (ERK1/2). ERK1/2 inhibitor could rescue phosphorylation of C-FOS and C-Jun, increased protein stability of C-Jun, and increased MMP9 expressions. Thus, our study demonstrated that high glucose could activate ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic skin and HaCaT cells.

• Authors: Jiangli Lang, Chen Yang, Lixuan Liu, Li Li, Liangyan Wu, Yanyan Liu, Hengli Luo, Li Yan, Sifan Chen, Jie Ning, Chuan Yang
• Journal: Experimental cell research (Exp Cell Res) Vol. 403 Issue 1 Pg. 112550 (06 01 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 33675806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Transcription Factor AP-1
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 9
• Glucose

Topics

• Animals
• Diabetes Mellitus (drug therapy)
• Diabetic Foot (drug therapy, metabolism)
• Glucose (pharmacology)
• Humans
• JNK Mitogen-Activated Protein Kinases (drug effects, metabolism)
• MAP Kinase Signaling System (drug effects)
• Matrix Metalloproteinase 9 (metabolism)
• Mitogen-Activated Protein Kinases (drug effects, metabolism)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (drug effects, metabolism)
• Up-Regulation (drug effects)
• Rats