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Details for anatomical structure: kidney

EndoNet ID: ENC00063

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Synonyms

kidney, , Ren

General information

Each of a pair of organs, presiding over the excretion of urea, uric acid and various other waste products of metabolism; it also contributes to the regulation of the osmotic equilibrium of the hydro-saline balance of the organism

Links to other resources

Cytomer cy0048389

Larger structures

    Substructures

      Secreted hormones

      • Hormone: calcitriol

        • Calcidiol hydroxylates in kidneys into calcitriol. [1]
        • The PTH receptor in the kidneys activates mitochondrial vitamin D1 alpha-hydroxylase, leading to increased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which, in turn, is a potent inducer of intestinal calcium absorption and bone resorption. [2]

        Influenced by:

        • PTHR1
          in kidney
        • VDR
          in kidney
          • The synthesis of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is most strongly regulated by dietary calcium and the action of parathyroid hormone to increase 1α-hydroxylase (1α-OHase) and decrease 24-hydroxylase (24-OHase) in kidney proximal tubules. [3]
          • 1,25-(OH)2D3 synthesis, induced by dietary calcium restriction, is also the result of negative feedback regulation blockade. [4]
          • Tissue-specific down-regulation of VDR by hypocalcemia blocks the 1,25-(OH)2D3 suppression of the 1α-OHase and upregulation of the 24-OHase in the kidney, causing a marked accumulation of 1,25-(OH)2D3 in the plasma. [4]
          • VDR clearly mediates the induction of the 24-OHase and the suppression of the 1α-OHase by 1,25-(OH)2D3. [5]
          • Thus, the PTH secreted under hypocalcemic conditions causes unbridled 1α-OHase activity in kidney and completely suppresses the 24-OHase activity causing high levels of 1,25-(OH)2D3 in the circulation. [6]
          • The accumulation of 1,25-(OH)2D3 in the plasma is because of high rates of production and an absence of renal degradation. This impressive regulation only serves to ensure high rates of calcium mobilization from bone as needed for soft tissue needs such as growth as shown by bone ash and skeletal density determinations. [4]
          • Loss of renal VDR interferes with the otherwise normal ability of 1,25-(OH)2D3 to exert negative feedback suppression on 1α-OHase. It, therefore, appears that the basis of this regulatory series of events rests with the regulation of VDR expression in renal and perhaps parathyroid cells by ambient calcium concentrations. [4]
      • Hormone: pentraxin 3

        • Human renal epithelial cells produce the long pentraxin PTX3. [7]
        • Interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) stimulation strongly enhance the expression and production of PTX3 in PTECs in a dose- and time-dependent manner. [7]
      • Hormone: lipocalin 2

        • NGAL was found in a variety of normal and pathological human tissues (cell type-specific pattern of expression in bronchus, stomach, small intestine, pancreas, kidney, prostate gland, and thymus). [8]
      • Hormone: erythropoietin

      • Hormone: LIF

        • The ureteric bud expressed LIF, and metanephric mesenchyme expressed its receptors. [9]
      • Hormone: CNTF

        • CNTF mRNA is widely expressed in the brain, heart, lung, liver, kidney and testis of the rat, in addition to preferential expression in the sciatic nerve. [10]
      • Hormone: C-C motif chemokine 2

        • Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells. [11]
      • Hormone: nephronectin

      • Hormone: IL-18

        • Upregulation of epithelial IL-18 plays an important role in immune and immunopathological reactions in renal parenchyma and contributes to rejection mechanisms of kidney allograft. [12]
      • Hormone: IL-15

      • Hormone: PDGFD

      • Hormone: MIP-3 beta

      • Hormone: hepcidin

      • Hormone: BMP7

      • Hormone: BMP4

      • Hormone: GAS-2

      • Hormone: AGRP

      • Hormone: atrial natriuretic factor

      • Hormone: galectin-1

      • Hormone: sFRP-3

      • Hormone: sclerostin

      • Hormone: laminin alpha-5 chain

      • Hormone: sNRP1

      • Hormone: TNFSF18

      • Hormone: APOD

      • Hormone: semaphorin 3F

      • Hormone: humanin

      • Hormone: WISP1

      • Hormone: WISP3

      • Hormone: NOV

      • Hormone: fractalkine

      • Hormone: SEMA4D

      • Hormone: CXCL16

      • Hormone: laminin alpha-1 chain

      • Hormone: renin

        • Juxtaglomerular cells in the kidney release the enzymatic hormone renin.

        Influenced by:

        • renin receptor
          in kidney
          • The (pro)renin receptor binds both renin and prorenin and is reported to increase the catalytic efficiency of renin and activate prorenin. [13]
          • Thus, binding of renin and prorenin not only stimulates the (pro)renin receptor but also increases angiotensin II formation, leading to angiotensin II type 1 receptor stimulation. [14]
        • Succinate receptor 1
          in kidney
          • Succinate has been shown to cause renin release from the kidney [15]
      • Hormone: MSMB

      • Hormone: PD-L1

      • Hormone: BD-1

      • Hormone: ECM1a

      • Hormone: EGF

      • Hormone: insulin-like peptide INSL5

      • Hormone: vasorin

      • Hormone: TIP39

        • Whether TIP39 acts as a competitor of P1R or as an activator for P2R in these tissues is unclear at present. [16]
        • Furthermore, there was evidence for TIP39 mRNA synthesis in fetal liver, kidney and heart.No response was detected in adult liver, lung, placenta and adrenal gland. [16]
      • Hormone: GnRH-II (Isoform 1)

      • Hormone: FAM3B-b

      • Hormone: FGF-23

      • Hormone: angiotensin II

        Influenced by:

        • angiotensin II type 1 receptor
          in proximal_tubule_of_nephron
          • Autocrine positive angiotensin II feedback: angiotensin II upregulates angiotensinogen mRNA expression, mediated via angiotensin type 1 receptor [17]
        • angiotensin II type 1 receptor
          in fibroblast
          • In renal interstitial fibroblasts angiotensin II up-regulates angiotensinogen gene expression, thereby causing hyperplasia and extracellular matrix production via tha angiotensin type 1 receptor. [18]
        • renin receptor
          in kidney
          • Renin binding to the renin receptor in the kidney secretes angiotensin 1 which is converted to angiotensin 2 [19]
      • Hormone: prostasin

        • We report that endogenous mouse prostasin is glycosylphosphatidylinositol (GPI) anchored to the cell surface and is constitutively secreted from the apical surface of kidney cortical collecting duct cells. [20]
        • We show that prostasin secretion depends on GPI anchor cleavage by endogenous GPI-specific phospholipase D1 (Gpld1). [20]

      Receptors

      • Receptor: V2

        Induced phenotype:

        • X-linked nephrogenic diabetes insipidus
          • Nephrogenic diabetes insipidus is characterised by the failure of the kidney to respond to arginine vasopressin (AVP) because of a receptor or postreceptor defect, despite raised serum concentrations of AVP. [21]
      • Receptor: V1b

      • Receptor: GL-R

        Induced phenotype:

        • regulation of ion transport and electrolyte excretion
      • Receptor: mineralcorticoid receptor

        Induced phenotype:

        • Hypoaldosteronism
          • Hypoaldosteronism (mineralocorticoid defiency) may be due to inadequate stimulation of aldosterone secretion (hyporeninemic hypoaldosteronism), defects in adrenal synthesis of aldosterone, or resistance to the ion transport effects of aldosterone, such as are seen in pseudohypoaldosteronism type I. [22]
        • Primary Hyperaldosteronism
          • Primary aldosteronism, the most common form of endocrine hypertension is characterized by autonomous aldosterone production by the adrenal cortex (unilateral disease caused by aldosterone-producing adenoma and less frequently by unilateral adrenal hyperplasia; bilateral disease caused by idiopathic adrenal hyperplasia) resulting in hypertension with suppressed plasma renin, and, less frequently, in hypokalemia. [23]
      • Receptor: PPARgamma1

        • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [24]
      • Receptor: sst1

      • Receptor: sst2

      • Receptor: CaSR

        Induced phenotype:

        • inhibition of the reabsorption of renal mineral ions
          • The CaSR has an inhibitory effect on the reabsorption of calcium, potassium, sodium and water in all nephron segments except for the proximal tube. [25]
      • Receptor: galanin receptor 2

      • Receptor: dopamine receptor D1

      • Receptor: dopamine receptor D4

      • Receptor: VDR

        Induced phenotype:

        • phosphate ion homeostasis
          • The homeostasis of serum Pi levels is effected through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. [26]
          • These processes are primarily regulated by 1-alpha,25-dihydroxyvitamin D [1,25(OH)2D3]. [27]
        • Secondary hyperparathyroidism
          • Chronic renal failure is the most common cause of secondary hyperparathyroidism. Failing kidneys do not convert enough vitamin D to its active form, and they do not adequately excrete phosphorus. [28]

        Influences:

        • calcitriol
          • The synthesis of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is most strongly regulated by dietary calcium and the action of parathyroid hormone to increase 1α-hydroxylase (1α-OHase) and decrease 24-hydroxylase (24-OHase) in kidney proximal tubules. [3]
          • 1,25-(OH)2D3 synthesis, induced by dietary calcium restriction, is also the result of negative feedback regulation blockade. [4]
          • Tissue-specific down-regulation of VDR by hypocalcemia blocks the 1,25-(OH)2D3 suppression of the 1α-OHase and upregulation of the 24-OHase in the kidney, causing a marked accumulation of 1,25-(OH)2D3 in the plasma. [4]
          • VDR clearly mediates the induction of the 24-OHase and the suppression of the 1α-OHase by 1,25-(OH)2D3. [5]
          • Thus, the PTH secreted under hypocalcemic conditions causes unbridled 1α-OHase activity in kidney and completely suppresses the 24-OHase activity causing high levels of 1,25-(OH)2D3 in the circulation. [6]
          • The accumulation of 1,25-(OH)2D3 in the plasma is because of high rates of production and an absence of renal degradation. This impressive regulation only serves to ensure high rates of calcium mobilization from bone as needed for soft tissue needs such as growth as shown by bone ash and skeletal density determinations. [4]
          • Loss of renal VDR interferes with the otherwise normal ability of 1,25-(OH)2D3 to exert negative feedback suppression on 1α-OHase. It, therefore, appears that the basis of this regulatory series of events rests with the regulation of VDR expression in renal and perhaps parathyroid cells by ambient calcium concentrations. [4]
      • Receptor: glucocorticoid receptor

      • Receptor: GR-beta

      • Receptor: ER-alpha

        Induced phenotype:

        • diabetic glomerulosclerosis
          • Estrogen via stimulation of ER alpha activates signaling pathways and regulates gene in glomerular/mesangiel clls in a manner that is protective against glomerulosclerosis. [29]
          • Estrogen deficiency accelerates the progression of the development of glomerulosclerosis. [30]
      • Receptor: PTHR1

        Induced phenotype:

        • phosphate ion homeostasis
          • The homeostasis of serum Pi levels is effected through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. [26]
          • These processes are primarily regulated by parathyroid hormone (PTH). [31]
        • familial isolated hypoparathyroidism
          • Familial isolated hypoparathyroidism can be caused by mutation in the parathyroid hormone gene. [32]
        • Primary hyperparathyroidism
          • Primary hyperparathyroidism is a relatively common endocrine disorder caused by abnormal regulation and hyper‐secretion of parathyroid hormone (PTH) from the parathyroid glands. [33]

        Influences:

        • calcitriol
      • Receptor: Tie2

      • Receptor: EP1

      • Receptor: EP3

      • Receptor: EP4

      • Receptor: angiotensin II type 1 receptor

        Induced phenotype:

        • salt and fluid balance
          • AT1 receptors are principially involved in the regulation of salt and fluid balance. [34]
        • renal water reabsorption
          • AT1 mediates reneal water reabsorption through Ang2 [19]
        • blood pressure increase
        • negative regulation of natriuresis
          • In the kidney, activation of AT1 receptors is associated with renal vasoconstriction and antinatriuresis. [35]
        • regulation of blood pressure
          • Renal AT1 receptors have unique and nonredundant actions in blood pressure homeostasis. [36]
          • Blood pressure is regulated by direct effects of AT1 receptors on kidney cells, independent of any impact of mineralocorticoids. [36]
      • Receptor: leptin receptor

        Induced phenotype:

        • positive regulation of diuresis by pressure natriuresis
          • Intravenous administration of leptin for five days to normal rats stimulated a diuresis with urine volumes being twice normal. [37]
          • Administration of leptin directly into the renal artery stimulated a natriuresis but not a kaliuresis suggesting an effect of leptin at the level of the collecting tubule. [38]
      • Receptor: B-CAM

      • Receptor: frizzled 1

      • Receptor: frizzled 9

      • Receptor: frizzled 2

      • Receptor: frizzled 8

      • Receptor: PTC1

      • Receptor: neuropilin 1

        Induced phenotype:

        • inhibition of ureteric bud branching
          • Sema3a inhibits ureteric bud brancing by downregulation of glia-cell-line-derived neurotrophic factor. [39]
        • excess of endothelial cells
          • Sema3a gene deletion causes excess endothelial cells. [40]
        • podocyte differentiation
          • Downregulation of WT1 and nephrin by Sema3a overexpression, and downregulation of PAX2 in Sema3a-/- mice, suggest that Sema3a might function as a modifier of PAX2 and WT1 signaling during podocyte differentiation. Thus, Sema3a may act as a negative regulator of podocyte differentiation pathways by inducing downregulation of WT1 and nephrin. [40]
        • cell differentiation
          • Sema3a overexpression in podocytes during kidney organogenesis leads to abnormal podocyte differentiation with a complete absence of slit diaphragms. [40]
          • Podocyte effacement might represent a final common pathway that occurs with disruption of podocyte differentiation. [40]
        • acute nephrotic range proteinuria
          • Administration of recombinant Sema3a to wild-type mice induces foot process effacement and fusion, endothelial cell swelling and reversible albuminuria, representing a novel mechanism for proteinuria.
      • Receptor: NPY4-R

      • Receptor: PLXND1

      • Receptor: TNFRSF12A

      • Receptor: Vascular endothelial growth factor receptor 1

      • Receptor: sVEGF-R1

      • Receptor: renin receptor

        • High levels found in the heart, brain, placenta, and lower levels in the kidney and liver. [13]

        Influences:

        • renin
          • The (pro)renin receptor binds both renin and prorenin and is reported to increase the catalytic efficiency of renin and activate prorenin. [13]
          • Thus, binding of renin and prorenin not only stimulates the (pro)renin receptor but also increases angiotensin II formation, leading to angiotensin II type 1 receptor stimulation. [14]
        • angiotensin II
          • Renin binding to the renin receptor in the kidney secretes angiotensin 1 which is converted to angiotensin 2 [19]
      • Receptor: VPAC1

        Induced phenotype:

        • positive regulation of vasodilation
          • The vasodilatory activity of PACAP has been documented in various organs including the kidney. [41]
      • Receptor: hepatocyte growth factor receptor

      • Receptor: RXR-alpha

      • Receptor: LXR-alpha

      • Receptor: IL-10R-alpha

      • Receptor: PPAR-alpha

        • PPARα is expressed at high levels in organs that carry out significant catabolism of fatty acids such as the brown adipose tissue, liver, heart, kidney, and intestine [42]
      • Receptor: LRP5

      • Receptor: fibroblast growth factor receptor-like 1

      • Receptor: integrin alpha-V/beta-5

      • Receptor: vasorin

      • Receptor: oxoeicosanoid receptor 1

      • Receptor: CRF-R1

      • Receptor: CHRNA1-2

      • Receptor: MRC2

      • Receptor: angiotensin receptor 2

      • Receptor: Succinate receptor 1

        Influences:

        • renin
          • Succinate has been shown to cause renin release from the kidney [15]
      • Receptor: beta-1 adrenoreceptor

        Influences:

        • renin
          • renin secretion from juxtaglomerular cells is mediated by the action on β1-adrenoreceptors of norepinephrine released from renal sympathetic nerve terminals as a result of renal nerve activity [43]
      • Receptor: PLXNB1

      • Receptor: NPY6-R

      • Receptor: PRLR

        Induced phenotype:

        • multicellular organismal water homeostasis
          • PRL is clearly involved in water and electrolyte balance in almost all classes of vertebrates, PRLRs are present in kidney, as well as other tissues involved in salt balance. [44]
        • reduction of electrolyte excretion
          • PRL plays a major role in regulating water and electrolyte balance through the kidney by stimulation of Na+-K+-ATPase and reduction of Na+ and K+ excretion. [45]
      • Receptor: Sphingosine 1-phosphate receptor 3

      • Receptor: Lysophosphatidic acid receptor 1

        Induced phenotype:

        • fibrosis
          • Fibrosis, the formation of excess fibrous connective tissues, is associated with a number of pathological conditions. Recently, a new aspect of LPA1 signaling has been uncovered in tubulointerstitial fibrosis (TIF), suggesting LPA1 signaling as a new therapeutic target in this disease. [46]
          • Likewise, in a unilateral ureteral obstruction model for TIF, the resulting kidney fibrosis was accompanied by an increase in LPA accumulation and LPA1 expression. [46]
          • Fibrosis was markedly reduced in Lpar1−/− mice or following treatment with Ki16425, an LPA1/LPA3 antagonist. [46]
      • Receptor: Lysophosphatidic acid receptor 3

      • Receptor: Ovarian cancer G-protein coupled receptor 1

      • Receptor: G-protein coupled receptor 4

      • Receptor: Lysophosphatidic acid receptor 2

      • Receptor: Lysophosphatidic acid receptor 4

      • Receptor: Sphingosine 1-phosphate receptor 1

      • Receptor: Sphingosine 1-phosphate receptor 2

      • Receptor: relaxin receptor 2

      • Receptor: 5-HT-2B

        Induced phenotype:

        • renal system process involved in regulation of blood volume
          • Central 5-HT2B receptors may play a selective role in the control of sympathetic supply to the kidney, which could be important in the central mechanisms involved in blood volume regulation. [47]
          • Activation of 5-HT-2B receptor subtypes mediate renal sympathoexcitation and hypotension. [47]
      • Receptor: PPAR beta/delta

        • A study with human tissues showed that PPARä was present in liver, intestine, kidney, abdominal adipose, and skeletal muscle, tissues that are all involved in aspects of lipid metabolism [24]
      • Receptor: NPR1

        • Human and rat NPR-A mRNA are highly expressed in kidney. [48]

        Induced phenotype:

        • natriuresis
          • ANP-dependent diuresis and natriuresis are mediated exclusively by NPR-A in mice because these effects are completely lost in NPR-A knockout animals. [48]
        • diuresis
          • ANP-dependent diuresis and natriuresis are mediated exclusively by NPR-A in mice because these effects are completely lost in NPR-A knockout animals. [48]

        Influences:

        • renin
          • In humans and experimental animals, administration of atrial natriuretic peptide (ANP) decreases plasma aldosterone levels by inhibiting renin secretion. [49]
          • ANP decreases renin secretion from the juxtaglomerular cells via a PKGII-dependent process (NPR1-involved). [48]
      Reference