Expression of transcellular and paracellular calcium and magnesium transport proteins in renal and intestinal epithelia during lactation

Am J Physiol Renal Physiol. 2017 Sep 1;313(3):F629-F640. doi: 10.1152/ajprenal.00680.2016. Epub 2017 May 24.

Abstract

Significant alterations in maternal calcium (Ca2+) and magnesium (Mg2+) balance occur during lactation. Ca2+ is the primary divalent cation mobilized into breast milk by demineralization of the skeleton and alterations in intestinal and renal Ca2+ transport. Mg2+ is also concentrated in breast milk, but the underlying mechanisms are not well understood. To determine the molecular alterations in Ca2+ and Mg2+ transport in the intestine and kidney during lactation, three groups of female mice consisting of either nonpregnant controls, lactating mice, or mice undergoing involution were examined. The fractional excretion of Ca2+, but not Mg2+, rose significantly during lactation. Renal 1-α hydroxylase and 24-OHase mRNA levels increased markedly, as did plasma 1,25 dihydroxyvitamin D levels. This was accompanied by significant increases in intestinal expression of Trpv6 and S100g in lactating mice. However, no alterations in the expression of cation-permeable claudin-2, claudin-12, or claudins-15 were found in the intestine. In the kidney, increased expression of Trpv5 and Calb1 was observed during lactation, while no changes in claudins involved in Ca2+ and Mg2+ transport (claudin-2, claudin-14, claudin-16, or claudin-19) were found. Consistent with the mRNA expression, expression of both calbindin-D28K and transient receptor potential vanilloid 5 (TRPV5) proteins increased. Colonic Trpm6 expression increased during lactation, while renal Trpm6 remained unaltered. In conclusion, proteins involved in transcellular Ca2+ and Mg2+ transport pathways increase during lactation, while expression of paracellular transport proteins remained unchanged. Increased fractional Ca2+ excretion can be explained by vitamin D-dependent intestinal hyperabsorption and bone demineralization, despite enhanced transcellular Ca2+ uptake by the kidney.

Keywords: TRPM6; TRPV5; calbindin; claudin; kidney.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adaptation, Physiological
  • Animals
  • Biological Transport
  • Calbindin 1 / genetics
  • Calbindin 1 / metabolism
  • Calcium / metabolism*
  • Calcium / urine
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Claudins / genetics
  • Claudins / metabolism
  • Epithelial Cells / metabolism*
  • Female
  • Intestinal Absorption
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Kidney / cytology
  • Kidney / metabolism*
  • Lactation / metabolism*
  • Magnesium / metabolism*
  • Mammary Glands, Animal / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Renal Reabsorption
  • S100 Calcium Binding Protein G / genetics
  • S100 Calcium Binding Protein G / metabolism
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Time Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamin D3 24-Hydroxylase / metabolism

Substances

  • Calb1 protein, mouse
  • Calbindin 1
  • Calcium Channels
  • Claudins
  • Membrane Transport Proteins
  • S100 Calcium Binding Protein G
  • S100g protein, mouse
  • TRPM Cation Channels
  • TRPV Cation Channels
  • Trpm6 protein, mouse
  • Trpv5 protein, mouse
  • Trpv6 protein, mouse
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Cyp24a1 protein, mouse
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Magnesium
  • Calcium

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