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SIRT1 reduction causes renal and retinal injury in diabetes through endothelin 1 and transforming growth factor β1.

Mortuza R, Feng B, Chakrabarti S - J. Cell. Mol. Med. (2015)

Bottom Line: Previously we showed glucose reduces sirtuin1 (SIRT1), a class III histone deacetylase.These cells also showed increased p300 expression, histone acetylation and reduced SIRT1 levels.These changes were rectified in the ECs following p300 silencing or by SIRT1 overexpression, whereas SIRT1 knockdown or p300 overexpression in NG mimicked the effects of HG.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.

No MeSH data available.


Related in: MedlinePlus

SIRT1 transgenic mice shows improved renal function and reduced oxidative stress and FN up-regulation with diabetes. (A) SIRT1 overexpression prevented diabetes-induced micro-albuminuria in mice. Furthermore, such overexpression averted diabetes-induced increased (B) collagen Iα(I) mRNA expression (C) FN protein and (D) total ROS/RNS levels in the renal and retinal tissues. Control = Non-diabetic wild-type, Co+SIRT1 Tg = SIRT1 transgenic mice non-diabetic, Diabetic = Wild-type diabetic, Di+SIRT1 Tg = SIRT1 transgenic mice diabetic, Co = Control, Di = Diabetic, * = significantly different from control, ╪ = significantly different from Diabetic. mRNA levels are expressed as a ratio of 18s. All data (mean ± SEM, P < 0.05) were normalized to Co; n = 8–10/group.
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fig06: SIRT1 transgenic mice shows improved renal function and reduced oxidative stress and FN up-regulation with diabetes. (A) SIRT1 overexpression prevented diabetes-induced micro-albuminuria in mice. Furthermore, such overexpression averted diabetes-induced increased (B) collagen Iα(I) mRNA expression (C) FN protein and (D) total ROS/RNS levels in the renal and retinal tissues. Control = Non-diabetic wild-type, Co+SIRT1 Tg = SIRT1 transgenic mice non-diabetic, Diabetic = Wild-type diabetic, Di+SIRT1 Tg = SIRT1 transgenic mice diabetic, Co = Control, Di = Diabetic, * = significantly different from control, ╪ = significantly different from Diabetic. mRNA levels are expressed as a ratio of 18s. All data (mean ± SEM, P < 0.05) were normalized to Co; n = 8–10/group.

Mentions: To examine the downstream consequence of SIRT1 mediated alteration of ET-1 and TGF-β1 in diabetes, we investigated urinary micro-albumin levels to assess renal function in these mice. Diabetic mice showed increased micro-albuminuria compared to controls indicating poor kidney function in these animals (Fig.6A). SIRT1 overexpression significantly reduced such micro-albuminuria in the transgenic diabetic animals (Fig.6A). Moreover histological analysis of renal tissues in these animals showed reduced mesangial expansion (a feature of diabetic nepthropathy) compared to the wild-type diabetic animals (Fig. S2C). Furthermore in the renal and retinal tissues of the diabetic animals such overexpression reduced diabetes-induced increased FN protein, total ROS/RNS and collagen Iα(I) mRNA expression levels (Fig.6B–D). These results suggest that SIRT1 has a protective role against diabetes-induced renal and retinal damages.


SIRT1 reduction causes renal and retinal injury in diabetes through endothelin 1 and transforming growth factor β1.

Mortuza R, Feng B, Chakrabarti S - J. Cell. Mol. Med. (2015)

SIRT1 transgenic mice shows improved renal function and reduced oxidative stress and FN up-regulation with diabetes. (A) SIRT1 overexpression prevented diabetes-induced micro-albuminuria in mice. Furthermore, such overexpression averted diabetes-induced increased (B) collagen Iα(I) mRNA expression (C) FN protein and (D) total ROS/RNS levels in the renal and retinal tissues. Control = Non-diabetic wild-type, Co+SIRT1 Tg = SIRT1 transgenic mice non-diabetic, Diabetic = Wild-type diabetic, Di+SIRT1 Tg = SIRT1 transgenic mice diabetic, Co = Control, Di = Diabetic, * = significantly different from control, ╪ = significantly different from Diabetic. mRNA levels are expressed as a ratio of 18s. All data (mean ± SEM, P < 0.05) were normalized to Co; n = 8–10/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4549036&req=5

fig06: SIRT1 transgenic mice shows improved renal function and reduced oxidative stress and FN up-regulation with diabetes. (A) SIRT1 overexpression prevented diabetes-induced micro-albuminuria in mice. Furthermore, such overexpression averted diabetes-induced increased (B) collagen Iα(I) mRNA expression (C) FN protein and (D) total ROS/RNS levels in the renal and retinal tissues. Control = Non-diabetic wild-type, Co+SIRT1 Tg = SIRT1 transgenic mice non-diabetic, Diabetic = Wild-type diabetic, Di+SIRT1 Tg = SIRT1 transgenic mice diabetic, Co = Control, Di = Diabetic, * = significantly different from control, ╪ = significantly different from Diabetic. mRNA levels are expressed as a ratio of 18s. All data (mean ± SEM, P < 0.05) were normalized to Co; n = 8–10/group.
Mentions: To examine the downstream consequence of SIRT1 mediated alteration of ET-1 and TGF-β1 in diabetes, we investigated urinary micro-albumin levels to assess renal function in these mice. Diabetic mice showed increased micro-albuminuria compared to controls indicating poor kidney function in these animals (Fig.6A). SIRT1 overexpression significantly reduced such micro-albuminuria in the transgenic diabetic animals (Fig.6A). Moreover histological analysis of renal tissues in these animals showed reduced mesangial expansion (a feature of diabetic nepthropathy) compared to the wild-type diabetic animals (Fig. S2C). Furthermore in the renal and retinal tissues of the diabetic animals such overexpression reduced diabetes-induced increased FN protein, total ROS/RNS and collagen Iα(I) mRNA expression levels (Fig.6B–D). These results suggest that SIRT1 has a protective role against diabetes-induced renal and retinal damages.

Bottom Line: Previously we showed glucose reduces sirtuin1 (SIRT1), a class III histone deacetylase.These cells also showed increased p300 expression, histone acetylation and reduced SIRT1 levels.These changes were rectified in the ECs following p300 silencing or by SIRT1 overexpression, whereas SIRT1 knockdown or p300 overexpression in NG mimicked the effects of HG.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.

No MeSH data available.


Related in: MedlinePlus