In summary, we have uniquely demonstrated that high glucose increases MIP-3 alpha through a TGF beta 1 dependent pathway, suggesting the centrality of TGF-beta1 in both the inflammatory and previously demonstrated fibrotic responses in diabetic nephropathy.
These results demonstrate that TGF-β and miR-192 decrease autophagy in MMCs under diabetic conditions and this can be reversed by inhibition or deletion of miR-192, further supporting miR-192 as a useful therapeutic target for DN.
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.
Moreover, ECH inhibited the TGF-β1/Smads signaling pathway, downregulated fibronectin (FN), collagen IV, and alpha-smooth muscle actin (α-SMA) levels, and upregulated E-cadherin level in the db/db mice model of DN.
We examined whether DNA sequence variants in the TGF-beta1 gene are associated with advanced diabetic nephropathy among Caucasians with type 1 diabetes mellitus.
Mesangial cell gremlin mRNA levels were induced by high glucose, cyclic mechanical strain, and TGF-beta1 in vitro, and gremlin mRNA levels were elevated in the renal cortex of rats with streptozotocin-induced diabetic nephropathy in vivo. gremlin expression was observed in parallel with induction of bone morphogenetic protein-2 (BMP-2), a target for gremlin in models of cell differentiation.
In the present study, we examined expression of PKCbeta1, MAPK/ERK kinase (MEK) 1, MEK2, extracellular signal-regulated protein kinase (ERK) 1, ERK2, and TGF-beta1 mRNAs using renal tissue samples from kidneys affected by DN (N= 21) and from normal human kidney (NHK; N= 6).
Activation of transforming growth factor β1 (TGFB1)/SMAD3 signaling may lead to additional synthesis of collagen type IV (COL4), which is a major contributor to extracellular matrix (ECM) accumulation in diabetic nephropathy (DN).
In this study, we aimed to explore the effect of combination of Ginsenoside Rg1 and Astragaloside IV on oxidative stress and TGF-β1/Smads signaling in DN rats.
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.
No significant differences in the TNF-alfa , TGF-beta 1 (codon 25) genotype distribution between healthy controls and patients with diabetic nephropathy- or glomerulonephritis-associated ESRD were detected.
However, the anti‑fibrotic mechanisms of KMUP‑1 treatment in diabetic nephropathy in terms of cell biology and transforming growth factor-β1 (TGF‑β1) remain unclear.