Dataset Information


Heterogeneous Nuclear Ribonucleoprotein F Stimulates Sirtuin-1 Gene Expression and Attenuates Nephropathy Progression in Diabetic Mice.

ABSTRACT: We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress, and nephropathy at age 20 weeks compared with their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs. Sirtuin-1, Foxo3?, and catalase expression were significantly decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3? with downregulation of acetylated p53 expression and prevented downregulation of Sirtuin-1 and Foxo3? expression in IRPTCs by high glucose plus palmitate. Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of Foxo3? and downregulation of acetylated p53 expression. hnRNP F stimulated Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter. Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3? than nondiabetic kidneys. Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes.


PROVIDER: S-EPMC5482081 | BioStudies | 2017-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3266424 | BioStudies
2019-01-01 | S-EPMC6491582 | BioStudies
2019-01-01 | S-EPMC6721388 | BioStudies
2015-01-01 | S-EPMC4572079 | BioStudies
2018-01-01 | S-EPMC6304851 | BioStudies
2018-01-01 | S-EPMC6115662 | BioStudies
2019-01-01 | S-EPMC6857156 | BioStudies
2016-01-01 | S-EPMC4948868 | BioStudies
2019-01-01 | S-EPMC6731588 | BioStudies
1000-01-01 | S-EPMC5899163 | BioStudies