Abstract
The kidney is an important target of the renin‐ANG‐aldosterone system (RAAS). To date, several studies have demonstrated the existence of a local RAAS in various tissues, including the renal tissue. The mineralocorticoid aldosterone is known to play a critical role in the classical RAAS; however, its effect on mesangial cells (MCs) remains to be elucidated. Based on this, our aim was to investigate whether aldosterone stimulation can modulate the intracellular RAAS of immortalized human MCs by evaluating ANG‐converting enzyme (ACE)/ANG II/ANG II receptor type 1 (AT1) and ANG‐converting enzyme 2 (ACE2)/ANG (1‐7)/MAS receptor axes. To realise this, protein expression, enzyme activity, and immunofluorescence were performed under aldosterone stimulation and in the presence of the mineralocorticoid receptor (MR) antagonist spironolactone (SPI). We observed that high doses of aldosterone increase ACE activity. The effect of aldosterone on the catalytic activity of ACE was completely abolished with the pretreatment of SPI suggesting that the aldosterone‐induced cell injuries through ANG II release were attenuated. Aldosterone treatment also decreased the expression of MAS receptor, but did not alter the expression or the catalytic activity of ACE 2 and ANG (1‐7) levels. Spironolactone modulated the localization of ANG II and AT1 receptor and decreased ANG (1‐7) and MAS receptor levels. Our data suggest that both aldosterone and the MR receptor antagonist can modulate both of these axes and that spironolactone can protect MCs from the damage induced by aldosterone.
Highlights
Since 1898, when Tigerstedt and Bergman described renin for the first time (Tigerstedt and Bergman 1898), numerous studies have examined the physiological and pathological roles of the renin-ANG-aldosterone system (RAAS) (Ghazi and Drawz 2017)
We focused on the activity and expression of the components of (ACE)/angiotensin II (ANG II)/ANG II receptor type 1 (AT1) and ANG-converting enzyme 2 (ACE2)/ANG (1-7)/MAS receptor axes under aldosterone stimulation
Our data indicated that prolonged stimulation with a physiological dose (0.1 nmol/L) of aldosterone increased the viability of mesangial cells (MCs) by approximately 20% compared with the control group and 10 nmol/L aldosterone treatment (Fig. 1)
Summary
Since 1898, when Tigerstedt and Bergman described renin for the first time (Tigerstedt and Bergman 1898), numerous studies have examined the physiological and pathological roles of the renin-ANG-aldosterone system (RAAS) (Ghazi and Drawz 2017). Aldosterone is a mineralocorticoid critical to the classical RAAS, contributing to the control of the acid/base and sodium/potassium balance and affecting several tissues; its effect on the local RAAS of mesangial cells (MCs) has not yet been described (Quinn and Williams 1988; Spat and Hunyady 2004). The embryological and morphological origin of MCs are the same as that of smooth muscle cells, with microfilaments associated with a-actin, myosin, and tropomyosin in its cytoskeleton. Due to these features, MCs are able to contract and/or expand.
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