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Role of transcription factor acetylation in diabetic kidney disease.

Liu R, Zhong Y, Li X, Chen H, Jim B, Zhou MM, Chuang PY, He JC - Diabetes (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine/Nephrology, Mount Sinai School of Medicine, New York, NY.

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Acetylation of p65 and STAT3 is increased in diabetic kidneys. A: Kidney sections from db/db and db/m mice were stained for acetyl-p65 and acetyl-STAT3 using specific antibodies. The representative pictures of six mice in each group are shown. B: Immunostaining was quantified as described in Research Design and Methods. *P < 0.01 compared with db/m mice (n = 6). COD, corrected optical density. C: Western blot analyses of glomerular lysates from db/db and db/m mice were performed for acetyl-, phosphor-, and total p65 and STAT3. The representative blots of three independent experiments are shown. D: Western blots from all experiments were quantified by densitometry analysis, as described in Research Design and Methods. The ratios of acetyl-protein or phosphor-protein to total protein were calculated for p65 and STAT3. The fold changes relative to db/m mice are shown. *P < 0.01 compared with db/m mice (n = 6). E: Kidney sections from nephrectomized samples of patients with normal kidneys, minimal change disease (MCD), and mild and advanced DN were stained for acetyl-STAT3 and NF-κB. The representative pictures are shown (n = 5). F: The quantitation data of immunostaining in kidney biopsies from patients with normal kidneys, MCD, mild DN, and advanced DN are shown. *P < 0.05 compared with normal and MCD (n = 5).
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Figure 1: Acetylation of p65 and STAT3 is increased in diabetic kidneys. A: Kidney sections from db/db and db/m mice were stained for acetyl-p65 and acetyl-STAT3 using specific antibodies. The representative pictures of six mice in each group are shown. B: Immunostaining was quantified as described in Research Design and Methods. *P < 0.01 compared with db/m mice (n = 6). COD, corrected optical density. C: Western blot analyses of glomerular lysates from db/db and db/m mice were performed for acetyl-, phosphor-, and total p65 and STAT3. The representative blots of three independent experiments are shown. D: Western blots from all experiments were quantified by densitometry analysis, as described in Research Design and Methods. The ratios of acetyl-protein or phosphor-protein to total protein were calculated for p65 and STAT3. The fold changes relative to db/m mice are shown. *P < 0.01 compared with db/m mice (n = 6). E: Kidney sections from nephrectomized samples of patients with normal kidneys, minimal change disease (MCD), and mild and advanced DN were stained for acetyl-STAT3 and NF-κB. The representative pictures are shown (n = 5). F: The quantitation data of immunostaining in kidney biopsies from patients with normal kidneys, MCD, mild DN, and advanced DN are shown. *P < 0.05 compared with normal and MCD (n = 5).

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.


Role of transcription factor acetylation in diabetic kidney disease.

Liu R, Zhong Y, Li X, Chen H, Jim B, Zhou MM, Chuang PY, He JC - Diabetes (2014)

Acetylation of p65 and STAT3 is increased in diabetic kidneys. A: Kidney sections from db/db and db/m mice were stained for acetyl-p65 and acetyl-STAT3 using specific antibodies. The representative pictures of six mice in each group are shown. B: Immunostaining was quantified as described in Research Design and Methods. *P < 0.01 compared with db/m mice (n = 6). COD, corrected optical density. C: Western blot analyses of glomerular lysates from db/db and db/m mice were performed for acetyl-, phosphor-, and total p65 and STAT3. The representative blots of three independent experiments are shown. D: Western blots from all experiments were quantified by densitometry analysis, as described in Research Design and Methods. The ratios of acetyl-protein or phosphor-protein to total protein were calculated for p65 and STAT3. The fold changes relative to db/m mice are shown. *P < 0.01 compared with db/m mice (n = 6). E: Kidney sections from nephrectomized samples of patients with normal kidneys, minimal change disease (MCD), and mild and advanced DN were stained for acetyl-STAT3 and NF-κB. The representative pictures are shown (n = 5). F: The quantitation data of immunostaining in kidney biopsies from patients with normal kidneys, MCD, mild DN, and advanced DN are shown. *P < 0.05 compared with normal and MCD (n = 5).
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Figure 1: Acetylation of p65 and STAT3 is increased in diabetic kidneys. A: Kidney sections from db/db and db/m mice were stained for acetyl-p65 and acetyl-STAT3 using specific antibodies. The representative pictures of six mice in each group are shown. B: Immunostaining was quantified as described in Research Design and Methods. *P < 0.01 compared with db/m mice (n = 6). COD, corrected optical density. C: Western blot analyses of glomerular lysates from db/db and db/m mice were performed for acetyl-, phosphor-, and total p65 and STAT3. The representative blots of three independent experiments are shown. D: Western blots from all experiments were quantified by densitometry analysis, as described in Research Design and Methods. The ratios of acetyl-protein or phosphor-protein to total protein were calculated for p65 and STAT3. The fold changes relative to db/m mice are shown. *P < 0.01 compared with db/m mice (n = 6). E: Kidney sections from nephrectomized samples of patients with normal kidneys, minimal change disease (MCD), and mild and advanced DN were stained for acetyl-STAT3 and NF-κB. The representative pictures are shown (n = 5). F: The quantitation data of immunostaining in kidney biopsies from patients with normal kidneys, MCD, mild DN, and advanced DN are shown. *P < 0.05 compared with normal and MCD (n = 5).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine/Nephrology, Mount Sinai School of Medicine, New York, NY.

Show MeSH
Related in: MedlinePlus