Mineralocorticoid receptor genetics: A scoping review

Table 1 Renal expression of mineralocorticoid receptor

Organ	Specie	Cellular location	Functional role
Kidney[12,13]	Human	Distal convoluted tubules and cortical collecting ducts	Aldosterone-dependent transepithelial sodium transport
Kidney[14]	Rat	Mesangial cells	Cell proliferation and micromechanical properties
Kidney[15]	Rat	Mesangial cells	Reactive oxygen species induced by aldosterone
Kidney[16]	Rat	Podocytes	Induction of oxidative stress

Table 2 Epithelial expression of mineralocorticoid receptor

Organ	Specie	Cellular location	Functional role
Colon[17-19]	Rat, human, chicken	Enterocyte	Transepithelial Na+ and water transport
Airway[20]	Rat	Trachea to bronchioles	ND
Salivary glands[21]	Rat	Parotid	ND
Sweat glands[22]	Human	Duct epithelial cells	Na+ and K+ sweat composition and prevents excessive salt loss during heat acclimatization
Skin[22]	Human	Keratinocytes, hair follicle	ND
Skin[23]	Mouse	Keratinocytes	Restrains keratinocyte proliferation and fine-tunes differentiation to maintain epidermal balance
Skin[24]	Mouse	Keratinocytes	Keratinocyte-specific anti-inflammatory action, by inhibiting NF-κB and STAT3 pathways
Skin[25]	Mouse	Keratinocytes	Normal keratinocyte motility and dermal remodeling during wound repair

ND: Not described.

Table 3 Ear and blood expression of mineralocorticoid receptor

Organ	Specie	Cellular location	Functional role
Inner ear[26]	Rat	Marginal cells of the stria vascularis and spiral ganglion neurons	Regulates endolymph homeostasis by controlling Na+/K+-ATPase activity
Inner ear[27,28]	Guinea pig	Lateral wall of the cochlea basal turn and the ampullae of the semicircular canals	ND
Inner ear[29]	Mouse	Ampulla epithelial cells of semicircular canal	Expressed functional MR and 11β-HSD2; promoted Na+ absorption and K+ secretion through the IsK/KvLQT1 channel
Blood[30-33]	Human	Mononuclear leukocytes	Intracellular Na+/K+ balance
			Induces oxidative stress (↑ p22phox); and upregulates PAI-1 expression
			Induces trained immunity

ND: Not described; MR: Mineralocorticoid receptor; PAI-1: Plasminogen activator inhibitor-1.

Table 4 Central nervous system expression of mineralocorticoid receptor

Organ	Specie	Cellular location	Functional role
CNS[34-37]	Rat	Hippocampus: Pyramidal neurons of CA1-CA4; granule cells of dentate gyrus	Increases neuronal excitability, facilitating action potential firing
CNS[38]	Mouse	Hippocampus: Pyramidal neurons of CA1-CA4; granule cells of dentate gyrus	Increases glutamate release, strengthening synaptic communication
CNS[39,40]	Mouse	Hippocampus: Pyramidal neurons of CA1-CA4; granule cells of dentate gyrus	Lower anxiety and regulation of the stress response
			Long-term survival and maintenance of mature granule neurons
CNS[41,42]	Rat	Hippocampus: Pyramidal neurons of CA1-CA4; granule cells of dentate gyrus	Inhibition progenitor proliferation
			Synaptic plasticity: Hippocampal long-term potentiation, memory formation, particularly under stress conditions
CNS[34-36]	Rat	Hypothalamus: Parvocellular and magnocellular neurons of PVN and ARC	ND

ARC: Arcuate nucleus; CA: Cornu ammonis; CNS: Central nervous system; ND: Not described; PVN: Paraventricular nucleus.

Table 5 Heart and cardiovascular system expression of mineralocorticoid receptor

Organ	Specie	Cellular location	Functional role
Heart[43-45]	Rat	Myocytes	Induces cardiomyocyte hypertrophy
Heart[46-48]	Mouse	Myocytes	Ventricular contractile dysfunction
			Increases ROS at and mitochondrial myocardial level, through the overexpression of NADPH oxidase
			Cardiac fibrosis and remodeling
			Apoptosis
Heart, blood vessels[49,50]	Rabbit	Myocytes; endothelial and vascular smooth muscle cells	Promotes endothelial dysfunction and oxidative stress in atherosclerosis
Heart, blood vessels[51]	Rat	Myocytes; endothelial and vascular smooth muscle cells	Promotes vascular smooth muscle cells proliferation

ROS: Reactive oxygen species.

Table 6 Adipose and ocular expression of mineralocorticoid receptor

Organ	Specie	Cellular location	Functional role
Adipose tissues[52-54]	Mouse	White adipocytes	Proadipogenic, promoting the differentiation of preadipocytes into mature fat cells
Adipose tissues[55-57]	Mouse	Brown adipocytes	Promotes differentiation and down-regulates UCP1 and UCP3 expression, contributing to the regulation of cellular energy expenditure
Retina[58-60]	Rat	Müller glial cells	Regulates Na+, K+ and water channel expression (ENaC-α, Kir4.1, AQP4)
Retina[58-60]	Rat/human	Choroid (vascular endothelium)	Choroidal vascular permeability and vasodilation by KCa23 channel regulation
Iris-ciliary body[61]	Rabbit	ND	ND

AQP: Aquaporin; ENaC: Epithelial sodium channel; Kir: Inwardly rectifying potassium channel; ND: Not described; UCP: Uncoupling protein.

Table 7 Interactions of mineralocorticoid receptors in non-aldosterone-bound states

Protein name	Type	Cellular compartment	Functional role
Hsp90	Chaperone	Cytoplasm	Maintaining MR in an appropriate conformation for ligand binding[107]
Hsp70, Hsp40, Hip(p48)	Chaperone and co-chaperone	Cytoplasm	Stabilize unliganded MR and assist in early complex assembly before Hsp90 recruitment[108-111]
Hop (p60), p23	Co-chaperone	Cytoplasm	Link Hsp70 and Hsp90 during MR complex assembly and stabilize the receptor-chaperone complex[108-111]
BAG-1	Co-chaperone (Hsp70-interacting protein)	Cytoplasm	Modulates MR transcriptional activity[112,113]
FKBP51, FKBP52, PP5	Immunophilins/TPR co-chaperones	Cytoplasm	Regulate receptor transport: FKBP51 impairs nuclear translocation; FKBP52 and PP5 facilitate dynein/dynactin-mediated retrograde transport toward the nucleus[108,111,114]
CyP40	Immunophilin	Cytoplasm and nucleus	TPR-domain co-chaperone that associates with HSP90 complexes; contributes to receptor-HSP90 assembly and may modulate receptor function through regulation of HSP90 ATPase activity[108,111,115]
XAP2/ARA9, WISp39	Immunophilin-like co-chaperones	Cytoplasm	Stabilization and assembly of the HSP90-MR complex[111]
Actin	Chaperone	Cytoplasm	Ligand-dependent nuclear translocation[109]
SRC-1, SRC-2, PGC1-α	Co-regulators (common co- activators)	Nucleus	Interact with LBD and RNA Pol II; enhance transcription through LxxLL motifs[116-119]
CBP/p300	Co-regulator (activator)	Nucleus	Interacts NTD and LBD, induces chromatin remodeling and histone acetylation[118-120]
ELL	Co-regulator (activator)	Nucleus	Potentiates MR activity while repressing GR[121]
HDAC3–4, HDAC5	Co-regulators (modulators)	Nucleus	Modulate MR acetylation and transcriptional activity[122]
RNA Helicase A	Co-regulator (activator)	Nucleus	Recruits CBP and enhances aldosterone-dependent MR transcription[123]
NCoR, SMRT, DAXX	Co-regulators (repressors)	Nucleus	Bind MR and repress its transcriptional function[118,124,125]
PIAS1	Co-regulator (repressor)	Nucleus	SUMOylates MR, repressing its transcriptional activity[71,121]
Rac1 (small GTPase)	Signal transducer	Cytoplasm	Activates MR in a ligand-independent manner (notably in kidney and heart)[87,126]
CHIP	E3 ubiquitin ligase	Cytoplasm	Promotes MR polyubiquitination and proteasomal degradation[127]

MR: Mineralocorticoid receptor; DBD: DNA-binding domain; LBD: Ligand-binding domain; NTD: N-terminal domain; GR: Glucocorticoid; CBP: CREB-binding protein; TPR: Tetratricopeptide repeat.