Changes in expression of special AT-rich sequence binding protein 1 and phosphatase and tensin homologue in kidneys of diabetic rats during ageing

Jukic, Ivana; Kostić, Sandra; Filipović, Natalija; Ensor, Larissa Gudelj; Ivandic, Marijeta; Dukic, Jozefina Josipa; Uljević, Marija Vitlov; Hamzić, Lejla Ferhatović; Puljak, Livia; Vukojević, Katarina

doi:10.1093/ndt/gfy003

Cited by 8 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33 Importantly, SATB1 expression was suggested to be significantly increased in diabetic rats two weeks after diabetes mellitus induction. 18 In a study by Vitlov et al, the authors also increased immunofluorescence intensity of SATB1 in the distal tubular cells in kidney tissues of the diabetic rats compared to the non-diabetic ones. 34 In the present study, we first confirmed the binding relationship between FOXA1 and SATB1 through luciferase and ChIP assays.…”

Section: Discussionmentioning

confidence: 90%

“…SATB1 is a nuclearmatrix-binding protein accountable for the regulation of tissue-specific chromatin structure and gene expression, and it has been observed to be upregulated in a rat model with DN. 18 Aberrant expression of SATB1 has also been reported to be relevant to several human cancers. 19,20 Here, we aimed to validate the possible interaction between FOXA1 and SATB1, and to explore their functions in DN progression using a mouse model with DN and high glucose (HG)-treated podocytes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FOXA1 Suppresses SATB1 Transcription and Inactivates the Wnt/β-Catenin Pathway to Alleviate Diabetic Nephropathy in a Mouse Model

Zhu¹,

Peng²,

Li³

2021

DMSO

View full text Add to dashboard Cite

Objective Diabetic nephropathy (DN) represents the most common diabetic complication that may lead to end-stage renal disease. This work focused on the effect of FOXA1 on the DN development and the molecular mechanism. Methods A mouse model of DN was induced by high-fat diets and streptozotocin. The concentrations of blood glucose and urinary protein in mice, and the pathological changes in mouse kidney tissues were determined. A podocyte cell line MPC-5 was treated with high glucose (HG) to mimic a DN-like condition in vitro. FOXA1 and SATB1 were overexpressed in HG-treated MPC-5 cells and in DN mice to explore their effects on cell proliferation and apoptosis, and on pathological changes in mouse kidney tissues. The binding relationship between FOXA1 and STAB1 was predicted and validated. Activation of the Wnt/β-catenin pathway was detected. Results FOXA1 was poorly expressed in the kidney tissues of DN mice. Overexpression of FOXA1 reduced the concentrations of fasting blood glucose and 24-h urinary protein in mice. It also suppressed the accumulation of glomerular mesangial matrix and hyperplasia of glomerular basement membrane, and reduced collagen deposition and interstitial fibrosis in mouse kidney. Also, FOXA1 reduced HG-induced apoptosis of MPC-5 cells. FOXA1 bound to the promoter region of SATB1 for transcription suppression. Overexpression of SATB1 activated the Wnt/β-catenin pathway and blocked the protective roles of FOXA1 in DN mice and in HG-treated MPC-5 cells. Conclusion This study demonstrated that FOXA1 transcriptionally suppresses SATB1 expression and inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting podocyte apoptosis and DN progression.

show abstract

Section: Discussionmentioning

confidence: 90%