4 research outputs found
Crosstalk between Aldosterone and Glycation through Rac‑1 Induces Diabetic Nephropathy
Background: Advanced glycation end products
(AGEs)
interaction with its receptor (RAGE) and aldosterone (Aldo) through
the mineralocorticoid receptor (MR) activates Rac-1 and NF-κB
independently in diabetic nephropathy (DN). However, the crosstalk
of Aldo with AGEs-RAGE is still unresolved. Our study examined the
impact of the AGEs-Aldo complex on renal cells and its effect on the
RAGE-MR interaction. Methods and results: Glycation of
human serum albumin (HSA) (40 mg/mL) with methylglyoxal (10 mM) in
the presence of Aldo (100 nM) and aminoguanidine (AG) (100 nM) was
performed. Glycation markers such as fructosamine and carbonyl groups
and fluorescence of AGEs, pentosidine, and tryptophan followed by
protein modification were measured. Renal (HEK-293T) cells were treated
with the glycated HSA-Aldo (200 μg/mL) along with FPS-ZM1 and
spironolactone antagonists for RAGE and Aldo, respectively, for 24
h. Glycation markers and esRAGE levels were measured. Protein and
mRNA levels of RAGE, MR, Rac-1, and NF-κB were estimated. Glycation
markers were enhanced with Aldo when albumin was only 14–16%
glycated. AGEs-Aldo complex upregulated RAGE, MR, Rac-1 and NF-κB
expressions. However, FPS-ZM1 action might have activated the RAGE-independent
pathway, further elevating MR, Rac-1, and NF-κB levels. Conclusion: Our study concluded that the presence of Aldo
has a significant impact on glycation. In the presence of AGEs-Aldo,
RAGE-MR crosstalk exerts inflammatory responses through Rac-1 in DN.
Insights into this molecular interplay are crucial for developing
novel therapeutic strategies to alleviate DN in the future