Rho-associated, coiled-coil-containing protein kinase 2 regulates expression of mineralocorticoid receptor to mediate sodium reabsorption in mice

Biochem Biophys Res Commun. 2024 Dec 3:736:150874. doi: 10.1016/j.bbrc.2024.150874. Epub 2024 Oct 23.

Abstract

The mineralocorticoid receptor (MR) is a member of the nuclear receptor family that was initially identified to regulate blood pressure through its ability to modulate kidney sodium handling in response to aldosterone. MR can be regulated by signals other than aldosterone; however, the detailed mechanisms remain to be elucidated. We found that MR is controlled in a Rho-associated coiled-coil-containing protein kinase 2 (ROCK2)-dependent manner. Mice with a specific deletion of ROCK2 in the kidney tubules showed decreased MR expression levels and increased urinary excretion of sodium. Mechanistically, signal transducer and activator of transcription 3 (STAT3) is a key molecule that mediates MR expression in these mice. This study highlights an important role of tubular ROCK2 in electrolyte homeostasis.

Keywords: Kidney tubules; Mineralocorticoid receptor; ROCK2; Rho-kinase.

MeSH terms

  • Aldosterone / metabolism
  • Animals
  • Gene Expression Regulation
  • Kidney Tubules / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Mineralocorticoid* / genetics
  • Receptors, Mineralocorticoid* / metabolism
  • Renal Reabsorption
  • STAT3 Transcription Factor / metabolism
  • Sodium* / metabolism
  • rho-Associated Kinases* / genetics
  • rho-Associated Kinases* / metabolism

Substances

  • Receptors, Mineralocorticoid
  • rho-Associated Kinases
  • Sodium
  • Rock2 protein, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Aldosterone