Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL)

Tetsuo Nishikawa, Sachiko Suematsu, Jun Saito, Akiko Soyama, Hiroko Ito, Tomoshige Kino, George Chrousos

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Systemic aldosterone plays an important role in the development of the microvascular disease and glomerular damage of the kidney in patients with diabetes mellitus and hyperlipidemia. Here, we investigated the possibility of local production of aldosterone in the kidney, using human primary glomerular mesangial cells. These cells produced both pregnenolone and aldosterone measured by specific radioimmunoassay and/or gas chromatography/mass spectrometry (GC/MS) methods. The production of both steroids was significantly stimulated by treatment with LDL, while angiotensin II had a synergistic effect. Adrenocorticotropic hormone (ACTH) and (Bu)2cAMP, on the other hand, failed to stimulate aldosterone production by these cells, suggesting that the local production of this steroid by mesangial cells is regulated differently from that of adrenal zona glomerulosa cells. Mesangial cells expressed the mRNA of the LDL receptor and steroidogenic enzymes, such as P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 21-hydroxylase and CYP11B2. Mesangial cells also expressed mRNA of the mineralocorticoid receptor (MR), and LDL stimulated its abundance by three-fold, while spironolactone, a completive antagonist of aldosterone, completely abolished this LDL effect. Since MR is a known mineralocorticoid-responsive gene as well as an intracellular receptor molecule for this steroid, these results suggest that locally produced aldosterone is biologically active, stimulating the transcription rates of the mineralocorticoid-responsive genes by activating the MR in mesangial cells. These pieces of evidence indicate that human mesangial cells are an aldosterone-producing tissue in which LDL plays a major regulatory role. Therefore, human renal mesangial endocrine system may contribute to local aldosterone concentrations and effects in the renal glomerulus independently of the systemic renin-angiotensin-aldosterone system and may participate in the development and progression of glomerular damage in several pathologic conditions.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume96
Issue number3-4
DOIs
Publication statusPublished - Aug 2005
Externally publishedYes

Fingerprint

Mesangial Cells
Aldosterone
LDL Lipoproteins
Mineralocorticoid Receptors
Zona Glomerulosa
Kidney
Mineralocorticoids
Steroids
3-Hydroxysteroid Dehydrogenases
Cytochrome P-450 CYP11B2
Mineralocorticoid Receptor Antagonists
Genes
Steroid 21-Hydroxylase
Pregnenolone
Messenger RNA
Spironolactone
Endocrine System
LDL Receptors
Steroid Receptors
Renin-Angiotensin System

Keywords

  • 21-Hydroxylase
  • 3β-HSD
  • Aldosterone
  • CYP11B2
  • LDL receptor
  • Low-density lipoprotein (LDL)
  • Mesangial cells
  • Mineralocorticoid receptor
  • P450scc
  • Pregnenolone

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). / Nishikawa, Tetsuo; Suematsu, Sachiko; Saito, Jun; Soyama, Akiko; Ito, Hiroko; Kino, Tomoshige; Chrousos, George.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 96, No. 3-4, 08.2005, p. 309-316.

Research output: Contribution to journalArticle

Nishikawa, Tetsuo ; Suematsu, Sachiko ; Saito, Jun ; Soyama, Akiko ; Ito, Hiroko ; Kino, Tomoshige ; Chrousos, George. / Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). In: Journal of Steroid Biochemistry and Molecular Biology. 2005 ; Vol. 96, No. 3-4. pp. 309-316.
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AU - Ito, Hiroko

AU - Kino, Tomoshige

AU - Chrousos, George

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