Angiotensin II Type 1 Receptor Modulation in Renal Physiology

The angiotensin II type 1 receptor (AT1R) is a G protein–coupled receptor central to the regulation of renal haemodynamics, tubular sodium transport and fluid balance. Upon binding of its ligand angiotensin II, AT1R activation triggers vasoconstriction of afferent and efferent arterioles, stimulates sodium reabsorption in proximal and distal nephron segments and promotes growth and inflammatory pathways within the kidney. Modulation of AT1R signalling occurs through multiple mechanisms, including receptor internalisation, biased agonism and interactions with accessory proteins. Angiotensin receptor antagonists and inverse agonists are established therapies for hypertension and nephropathy, yet emerging research highlights the potential to fine-tune receptor responses via endogenous modulators that preserve beneficial signalling while limiting pathological effects. Advances in our understanding of AT1R-associated proteins and downstream effectors have revealed new layers of control over receptor trafficking, post-translational modification and cross-talk with metabolic and ageing pathways. This expanding mechanistic insight holds promise for targeted interventions to mitigate kidney injury and improve global outcomes in chronic kidney disease.

Research from Nature Portfolio

Investigations using an immortalised human proximal tubule epithelial cell line have delineated the role of AT1R-associated protein (ATRAP) in maintaining sirtuin 1 (SIRT1) protein abundance. Knockdown of ATRAP led to a marked reduction in SIRT1 levels without altering its mRNA expression, implicating ATRAP in post-transcriptional regulation of this NAD+-dependent deacetylase. Given SIRT1’s established protective roles in cellular stress responses and ageing, these findings link AT1R modulation directly to renal epithelial resilience and suggest that enhancing ATRAP function may counteract age-associated decline in kidney function.

Angiotensin II Type 1 Receptor Modulation in Renal Physiology publication trend

The graph below shows the total number of articles in angiotensin ii type 1 receptor modulation in renal physiology across all publications each year (not limited to Nature Index journals).

Technical terms

Angiotensin II type 1 receptor (AT1R): A G protein–coupled receptor mediating most physiological and pathological actions of angiotensin II in the kidney and vasculature.

AT1R-associated protein (ATRAP): An intracellular adaptor that binds the receptor’s carboxyl-terminal domain to promote internalisation and attenuate pathological signalling.

Sirtuin 1 (SIRT1): A NAD+-dependent deacetylase involved in cellular stress resistance, metabolism and longevity pathways.

Calcium-modulating cyclophilin ligand (CAML): A protein that interacts with ATRAP to regulate calcineurin-NFAT signalling downstream of AT1R activation.

Nuclear factor of activated T cells (NFAT): A family of transcription factors activated by dephosphorylation via calcineurin, modulating expression of genes linked to inflammation and growth.

References

1. Cloning and Characterization of ATRAP, a Novel Protein That Interacts with the Angiotensin II Type 1 Receptor*. Journal of Biological Chemistry (1999).
2. Identification of Calcium-modulating Cyclophilin Ligand (CAML) as Transducer of Angiotensin II-mediated Nuclear Factor of Activated T Cells (NFAT) Activation*. Journal of Biological Chemistry (2005).
3. Angiotensin II type 1 receptor-associated protein deficiency attenuates sirtuin1 expression in an immortalised human renal proximal tubule cell line. Scientific Reports (2019).