Long-term inhibition and targeting TGFbeta(1) directly is problematic, therefore, a more fruitful direction targeting diabetic nephropathy may involve the development of therapeutic strategies specifically targeting CTGF.
Mechanistic studies in both in vivo and in vitro systems showed that the Nrf2-mediated protection against diabetic nephropathy is, at least, partially through inhibition of transforming growth factor-beta1 (TGF-beta1) and reduction of extracellular matrix production.
Excessive growth of glomerular mesangial cells and overexpression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) are the pathological features of diabetic nephropathy.
To our knowledge, this is the first genetic report highlighting the dual effects of TGF-beta1 in the onset of T1D as well as type 1 DN and can be a good model for extensive studies.
We established renal fibrosis model both in vitro with fibroblast cells treated with rhTGF-β1 and streptozocin(STZ)-induced diabetic nephropathy rats model in vivo and evaluated the effect of the aqueous extract of Lycopus lucidus Turcz, the blood-circulation-promoting Chinese herb, on diabetic nephropathy and investigated the mechanism of action.
Transforming growth factor-β1 and bone morphogenetic protein-7 (BMP7) have been shown to induce DN-like changes in the kidney and protect the kidney from such changes, respectively.
The aim of this study was to investigate the role of Nox4 inhibition on TGFβ1-induced fibrotic responses in proximal tubular cells and in a mouse model of diabetic nephropathy.
In conclusion, these preliminary data showed that the TGF-β1 codon 10 C allele, and C allele-containing genotypes may be susceptible, and T allele/TT genotype may be protective factors for T2D and DN(+) complications.
MicroRNAs (miRNAs), such as miR-192, mediate the actions of transforming growth factor-β1 (TGF-β) related to the pathogenesis of diabetic kidney diseases.
In the current paper we investigate the possible mechanisms for the involvement of NSA2 in diabetic nephropathy by testing the hypothesis that NSA2 expression is linked to the TGFβ1 pathway.
Although key signal transduction and gene regulation mechanisms have been identified, especially those related to the effects of hyperglycaemia, transforming growth factor β1 and angiotensin II, progress in functional genomics, high-throughput sequencing technology, epigenetics and systems biology approaches have greatly expanded our knowledge and uncovered new molecular mechanisms and factors involved in DN.
This review focuses on describing how, through reductionist in vitro experimentation focusing on TGF-β1-related responses to hyperglycaemia, we have identified induced in high glucose-1 (IHG-1), induced in high glucose-2 (IHG-2/Grem1) and the lipoxin-inducible microRNA let-7c as potential targets for harnessing new therapeutic approaches to limit the bioactivity of TGF-β1 in diabetic kidney disease.
The TT genotype of TGF-β1T869C in the overall population was associated with DN risk, whereas the CC genotype and T allele were distinctly associated with DN risk in the Asian population.