Receptor for advanced glycation end as drug targets in diabetes-induced skin lesion.
The involvement of the receptor for advanced glycation end (RAGE) in different diseases has been reviewed in great detail, previously, but the effects of diabetic drugs on RAGE-induced skin lesion during long course diabetes remains poorly understood. In the present study, we have shown that RAGE was overexpressed in both diabetic rats and human keratinocytes (HaCaT cells). Cell cycle arrest and apoptosis as well as alternations of relative protein levels were also found in diabetic rats and HaCaT cells with overexpression of RAGE that were rectified by metformin (Met) treatment. Moreover, overexpression of RAGE was also found to induce secretions of TNF-α, IL-1β, IL-6, ICAM-1 and COX-2 in HaCaT cells, and Met treatment corrected these inflammatory factor secretions. In addition, treatment with Met markedly reduced RAGE overexpression-induced p38 and NF-κB activation. Taken together, the findings of the present study have demonstrated, for the first time that Met protects HaCaT cells against diabetes-induced injuries and inflammatory responses through inhibiting activated RAGE.
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Xiang-Fang
XF
Chen
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Wei
W
Tang
Department of Burns, Shanghai Fire Corps Hospital Chinese People's Armed Police Shanghai 200443, China.
Wei-Dong
WD
Lin
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Zi-Yu
ZY
Liu
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Xiao-Xiao
XX
Lu
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Bei
B
Zhang
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Fei
F
Ye
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Zhi-Min
ZM
Liu
Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Jun-Jie
JJ
Zou
Department of Dermatology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Wan-Qing
WQ
Liao
Diabetes; RAGE; apoptosis; drug target; inflammatory response