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Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA

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Abstract

The migration and proliferation of keratinocytes is critical to wound re-epithelialization and defects in this function are associated with the clinical phenomenon of chronic non-healing wounds. Advanced glycation end products (AGEs) occur through non-enzymatic glycation of long-lived proteins in diabetes and play important roles in diabetic complications. However, specific roles for AGEs in keratinocyte migration and proliferation, and the underlying molecular mechanisms, have not been fully established. The aim of the current study was to elucidate the interaction between AGE-modified bovine serum albumin (AGE-BSA) and keratinocytes. As a result, we found that AGE-BSA had no effect on the viability of keratinocytes for up to 48 h of incubation with 50 μg/ml of AGE-BSA. AGE-BSA (but not non-glycated BSA) exerted a concentration-dependent suppression of keratinocyte migration at a range of concentrations. The expression of matrix metalloproteinase-9 (MMP-9) was significantly up-regulated in keratinocytes incubated with increasing AGE-BSA, but tissue inhibitor of metalloproteinases-1 (TIMP-1) expression was down-regulated. AGE-BSA also profoundly depressed phospho-focal adhesion kinase-Tyr397 (p-FAK) and α2β1 integrin expression, while total-FAK expression levels remained constant, in keratinocytes. The proliferative capacity of keratinocytes was diminished after 72 h AGE-BSA incubation. Taken together, these findings suggested that in the presence of AGE-BSA, keratinocytes lose their migratory and proliferation abilities. These data also indicated that, in the context of the chronic hyperglycemia in diabetes, the effects of AGE-BSA on keratinocyte migration might be mediated through MMP-9/TIMP-1, p-FAK and α2β1 integrin.

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Acknowledgments

This research was supported by the National Science Foundation of China (Grant No. 81070660) and the Science and Technology Foundation of Guangdong province (Grant No. 0321). We are grateful to Shao-ling Zhang for critical review of the manuscript.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, People’s Republic of China

    Ping Zhu, Chuan Yang, Li-Hong Chen, Meng Ren, Guo-juan Lao & Li Yan

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  1. Ping Zhu
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  2. Chuan Yang
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  3. Li-Hong Chen
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Correspondence to Li Yan.

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Zhu, P., Yang, C., Chen, LH. et al. Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA. Arch Dermatol Res 303, 339–350 (2011). https://doi.org/10.1007/s00403-010-1102-z

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