Related Experiment Video

Updated: Apr 26, 2026

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

1.1K

Nrf2 ameliorates diabetic nephropathy progression by transcriptional repression of TGFβ1 through interactions with

Pan Gao1, Liliang Li2, Lili Ji3

  • 1Department of Pathology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai, China.

Biochimica Et Biophysica Acta
|July 22, 2014
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (Nrf2) slows diabetic nephropathy (DN) progression by repressing transforming growth factor beta 1 (TGFβ1) via interactions with c-Jun and SP1. This mechanism offers potential therapeutic targets for DN.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Diabetic nephropathy (DN) is a severe complication of diabetes.
  • Reactive oxygen species (ROS) contribute to DN progression.
  • Nrf2 is a key transcription factor regulating antioxidant responses.

Purpose of the Study:

  • To investigate the role of Nrf2 in diabetic nephropathy progression.
  • To elucidate the regulatory mechanism of Nrf2 in DN.
  • To examine Nrf2's effect on TGFβ1 expression in renal cells.

Main Methods:

  • Utilized a mouse model of type II diabetes and cultured human renal mesangial cells (HRMCs).
  • Assessed Nrf2's transcriptional activity and its interaction with TGFβ1 promoter.
  • Employed c-Jun and SP1 knockdown and site-directed mutagenesis to study regulatory pathways.

Main Results:

  • Nrf2 ameliorates DN progression by repressing TGFβ1 transcription both in vivo and in vitro.
  • Nrf2 directly binds to the TGFβ1 promoter through interactions with c-Jun and SP1.
  • Knockdown of c-Jun or SP1, or mutagenesis of binding sites, abolished Nrf2-mediated TGFβ1 repression.
  • Nrf2 inhibits c-Jun and SP1 activation, thereby reversing their pro-TGFβ1 transcriptional effects.

Conclusions:

  • Nrf2 slows DN progression by repressing TGFβ1 in a c-Jun and SP1-dependent manner.
  • The findings provide novel insights into DN pathogenesis.
  • This pathway represents a potential target for clinical interventions in diabetic nephropathy.
Keywords:
Diabetic nephropathyNrf2ROSSP1TGFβ1c-Jun

Related Concept Videos

Diabetic Nephropathy01:28

Diabetic Nephropathy

Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration...
26
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.1K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
6.5K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.0K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.0K