Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications for impaired wound healing in patients with diabetes

Lan, C.‐C. E.; Liu, I.-H.; Fang, Ay-Huey; Wen, Chiyu; Wu, Ching‐Shuang

doi:10.1111/j.1365-2133.2008.08789.x

Cited by 120 publications

(145 citation statements)

References 90 publications

(154 reference statements)

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“…Immune dysfunctions that affect leukocyte adherence, chemotaxis and phagocytosis occur under hyperglycemic conditions and may make DM patients more prone to infections (5-7). We recently demonstrated that the physiologic functions of keratinocytes, the immune-competent cells that form the outermost layer of the skin, were also affected by high-glucose environments (8,9).…”

Section: Introductionmentioning

confidence: 99%

High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes

Lan

Huang

et al. 2011

Mol Med

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Diabetes mellitus is characterized by elevated plasma glucose and increased rates of skin infections. Altered immune responses have been suggested to contribute to this prevalent complication, which involves microbial invasion. In this study we explored the effects of a high-glucose environment on the innate immunity of keratinocytes by focusing on β defensin-3 (BD3) using in vivo and in vitro models. Our results demonstrated that the perilesional skins of diabetic rats failed to show enhanced BD3 expression after wounding. In addition, high-glucose treatment reduced human BD3 (hBD3) expression of cultured human keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end products. On the other hand, toll-like receptor-2 expression and function of cultured keratinocytes were not significantly affected by high-glucose treatment. In summary, high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes, which in turn contributed to the frequent occurrences of infection associated with diabetic wounding.

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Section: Introductionmentioning

confidence: 99%

High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes

Lan

Huang

et al. 2011

Mol Med

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“…For instance, Lerman et al (7) demonstrated that fibroblasts from diabetic mice migrated 75% less than those from normoglycemic mice and displayed a constant response to hypoxia, a condition commonly present in chronic wounds. Recently, an inhibition phenomenon similar to that in mice was observed in keratinocytes cultured in a high-glucose (HG) environment (8), which suggested that HG has a significant role in delaying wound repair. Mitogen-associated protein kinases (MAPKs) were identified to be involved in reactive oxygen species (ROS) production upon HG stress (9).…”

Section: Introductionmentioning

confidence: 99%

Nuclear factor-κB signaling negatively regulates high glucose-induced vascular endothelial cell damage downstream of the extracellular signal-regulated kinase/c-Jun N-terminal kinase pathway

Chen

Guo

Zheng

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Diabetes mellitus (DM)-induced high blood sugar severely damages vascular endothelial cells (VECs), which are in direct contact with the blood. Diabetic complications cause difficulties in skin wound healing and VECs are important for this process. Previous studies demonstrated that high blood sugar delayed the repair of wounded VECs, but the underlying mechanism has remained elusive. To explore the effects of diabetic conditions on VEC damage, cells were incubated in a medium with high glucose and then subjected to RNA-sequencing based transcriptome analysis. The results revealed that numerous biological processes were altered by HG stress, including extracellular matrix-receptor interaction, NOD-like receptor signaling and the nuclear factor (NF)-κB pathway. HG treatment increased the levels of phosphorylated inhibitor of NF-κB (IκB-α), the key NF-κB signaling regulator as well as the transcripts of plasminogen activator inhibitor-1 and interleukin-8, two inflammatory response markers. Treatment with extracellular signal-regulated kinase (ERK)-and c-Jun N-terminal kinase (JNK)-specific inhibitors U0126 and sp600125, respectively, led to the activation of IκB-α; however, the inhibitor of IκBα phosphorylation Bay11-7082 did not affect ERK and JNK activity, suggesting that ERK/JNK signaling occurs upstream of NF-κB in VECs. The present study provided useful information regarding the effects of diabetes on VECs, which may provide approaches for therapies of diabetes-associated complications in the future.

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“…Reduced keratinocyte migration is an important factor in impaired reepithelialization of chronic and diabetic healing (Stojadinovic et al, 2005;Lan et al, 2008;Usui et al, 2008;Jacobsen et al, 2010). We identified two distinct mechanisms through which FOXO1 affects keratinocyte migration, both of which are affected by diabetes in vivo and by high levels of glucose, an AGE, or TNF in vitro.…”

Section: Discussionmentioning

confidence: 97%

FOXO1 differentially regulates both normal and diabetic wound healing

Zhang¹,

Ponugoti²,

Tian³

et al. 2015

J Exp Med

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Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications for impaired wound healing in patients with diabetes

Cited by 120 publications

References 90 publications

High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes

High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes

Nuclear factor-κB signaling negatively regulates high glucose-induced vascular endothelial cell damage downstream of the extracellular signal-regulated kinase/c-Jun N-terminal kinase pathway

FOXO1 differentially regulates both normal and diabetic wound healing

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