Malnutrition delayed wound healing after tooth extraction by HMGB1-related prolonged inflammation

Yao Zhang,Hidetaka Ideguchi,Hiroaki Aoyagi,Keisuke Yamashiro,Tadashi Yamamoto,Masahiro Nishibori,Shogo Takashiba

doi:10.1016/j.intimp.2021.107772

Yao Zhang, Hidetaka Ideguchi + Show 5 more

Open Access

https://doi.org/10.1016/j.intimp.2021.107772

Copy DOI

Abstract

Malnutrition causes prolonged inflammation, resulting in delayed wound healing. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern that is present in the nuclei of macrophages and is secreted into the extracellular milieu in response to stimuli. It stimulates the production of interleukin-1β (IL-1β) through the receptors for advanced glycation end products (RAGE), inducing an inflammatory response, which is an essential response to initiate wound healing. We hypothesized that malnutrition may interfere with this cascade, causing abnormal inflammation and ultimately delaying wound healing. We used tooth-extracted mice with malnutrition fed with low-casein diet for two weeks. On days 3 and 7 after tooth extraction, the wound tissue was histologically observed and analyzed for several factors in the inflammation-regeneration lineage, including IL-1β, mesenchymal stem cells, myeloperoxidase activity, HMGB1, macrophage polarization, and adenosine 5-triphosphate (ATP). On day 7, delayed wound healing was observed with the following findings under malnutrition conditions: decreased mRNA expression of genes for regeneration and mesenchymal stem cell (MSC) accumulation, an obvious increase in myeloperoxidase and IL-1β mRNA expression, an increase in HMGB1 levels, and an increase in ATP concentration in tissues with elevated proportion of M2 macrophages. These results suggest that the significantly increased secretion of HMGB1 associated with the upregulated production of ATP and IL-1β secretion via the RAGE pathway may interfere with the resolution of inflammation and wound healing under the state of malnutrition.

Highlights

Through rapid global nutrition transition, an increasing proportion of individuals are exposed to malnutrition during their life course
When the mRNA expression of genes in mesenchymal stem cells (MSCs) and osteoblasts was detected by Quantitative reverse transcription-polymerase chain re action (qRT-PCR) (Fig. 2B), CD44 and Nanog mRNAs tended to be expressed in tooth-extracted socket wounds in the control group on day 3
There was little neovascularization or new bone formation in the extraction wound and a decrease in the percentage of MSCs in the immune cells in the malnourished mouse model, which indicates that healing of the extraction wound under malnutrition conditions is delayed

Summary

Introduction

Through rapid global nutrition transition, an increasing proportion of individuals are exposed to malnutrition during their life course. Malnutrition is a frequent and serious condition of multifactorial origin and is associated with adverse consequences. It is generally believed that insufficient protein intake accompanied by malnutrition damages the innate or acquired immune function by imposing a high metabolic load on a depleted capacity for homoeostasis [5]. It increases the risk of developing non-communicable diseases and long-term chronic inflammation, such as cardiovascular disease, atherosclerosis syndrome, and chronic kidney disease [5,6,7,8,9]. Poor oral health may affect food selection and nutritional intake, leading to malnutrition [10]. Malnutrition impairs wound healing and increases the risk of secondary infections [12]

Methods

Results

Conclusion