RRC ID 54766
Author Umehara T, Mori R, Mace KA, Murase T, Abe Y, Yamamoto T, Ikematsu K.
Title Identification of Specific miRNAs in Neutrophils of Type 2 Diabetic Mice: Overexpression of miRNA-129-2-3p Accelerates Diabetic Wound Healing.
Journal Diabetes
Abstract Neutrophils are involved in the first stage of acute inflammation. After injury, they are mobilized and recruited to the injured tissue. In diabetes, wound healing is delayed and aberrant, leading to excessive recruitment and retention of neutrophils that fail to promote angiogenesis and prolong inflammation. However, the exact pathological mechanisms of diabetic-derived neutrophils in chronic inflammation remain unclear. Here, miRNA profiling of neutrophils from bone marrow in type 2 diabetic mice was performed using a microarray. miRNAs regulate the posttranscriptional expression of target mRNAs and are important in countering inflammation-related diseases. Our study revealed that miRNAs exhibit differential expression in diabetic-derived neutrophils compared with non-diabetic-derived neutrophils, especially miR-129 family members. miR-129-2-3p directly regulated the translation of Casp6 and Ccr2, which are involved in inflammatory responses and apoptosis. Furthermore, miR-129-2-3p overexpression at the wound site of type 2 diabetic mice accelerated wound healing. These results suggest possible involvement of miR-129-2-3p in diabetic-derived neutrophil dysfunction and that retention kinetics of neutrophils and chronic inflammation may be initiated through miR-129-2-3p-regulated genes. This study characterizes changes in global miRNA expression in diabetic-derived neutrophils and systematically identifies critical target genes involved in certain biological processes related to the pathology of diabetic wound healing.
Volume 68(3)
Pages 617-630
Published 2019-3
DOI 10.2337/db18-0313
PII db18-0313
PMID 30523028
MeSH 3T3 Cells Animals B-Lymphocytes / metabolism Diabetes Mellitus, Experimental / metabolism* Diabetes Mellitus, Type 2 / metabolism* Diabetes Mellitus, Type 2 / physiopathology HL-60 Cells Humans In Situ Hybridization Inflammation / metabolism Macrophages / metabolism Male Mice Mice, Mutant Strains MicroRNAs / metabolism* Mutation / genetics Neutrophils / metabolism* Real-Time Polymerase Chain Reaction T-Lymphocytes / metabolism Wound Healing / genetics Wound Healing / physiology*
IF 7.199
Times Cited 6
Resource
Human and Animal Cells HL60(RCB0041)