Role of transcription factor acetylation in diabetic kidney disease.
Bottom Line: Here, we determined the roles of Sirt1 and the effect of NF-κB (p65) and STAT3 acetylation in DN.Our findings strongly support a critical role for p65 and STAT3 acetylation in DN.Targeting protein acetylation could be a potential new therapy for DN.
Affiliation: Department of Medicine/Nephrology, Mount Sinai School of Medicine, New York, NY.Show MeSH
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Mentions: We previously found that acetylation of FOXO4 was significantly increased in the kidney of diabetic db/db mice compared with nondiabetic db/m mice (9). Here, we demonstrated that staining of both acetyl-p65 and acetyl-STAT3 was significantly higher in glomeruli of diabetic db/db mice compared with those of nondiabetic db/m mice (Fig. 1A and B). Western blots of isolated glomeruli from these mice revealed a higher level of phosphorylation and acetylation for p65 and STAT3 in diabetic db/db mice compared with db/m mice (Fig. 1C and D and Supplementary Fig. 1). Immunostaining of kidney biopsy samples revealed that acetylation of p65 and STAT3 was increased in both glomerular and tubular compartments of kidneys of patients with DN compared with patients with minimal change disease and normal kidney tissues from nephrectomy patients (Fig. 1E and F). The clinical characteristics of these patients are summarized in Supplementary Table 2.
Affiliation: Department of Medicine/Nephrology, Mount Sinai School of Medicine, New York, NY.