Adrenomedullin (AM) and receptor-activity-modifying proteins in glomeruli with Thy.1 glomerulonephritis

Michitaka Matsumoto1, Shouichi Fujimoto, Shuji Iwatsubo

  • 1First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki, 889-1692 Japan.

Abstract

Insights

Adrenomedullin (AM) and its receptors (RAMPs) increased during the resolution of Thy.1 glomerulonephritis, not during peak proliferation. This suggests AM may help ameliorate kidney inflammation.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Immunology

Background:

  • Adrenomedullin (AM) exhibits antiproliferative and proapoptotic effects on mesangial cells in vitro.
  • Regulation of AM and its receptors in glomerulonephritis remains unclear.

Purpose of the Study:

  • To investigate the sequential changes in AM and its receptor (RAMP) expression and production in glomeruli during Thy.1 glomerulonephritis.

Main Methods:

  • Quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure mRNA expression.
  • Immunoradiometric assay (IRMA) to quantify AM protein levels.
  • Immunohistochemical staining to localize AM production.

Main Results:

  • AM and RAMP2 mRNA expression and AM protein levels were unchanged during the peak proliferation phase (day 7) of Thy.1 glomerulonephritis.
  • Significant increases in AM mRNA and protein were observed during the resolution phase (day 14).
  • AM production in mesangial cells was predominantly increased on day 14.

Conclusions:

  • Adrenomedullin (AM) and RAMPs increase during the resolution phase of Thy.1 glomerulonephritis, not during active proliferation.
  • The antiproliferative and proapoptotic actions of AM suggest a role in the amelioration of glomerulonephritis.

Related Concept Videos

Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Adrenergic Receptors (Adrenoceptors): Classification01:27

Adrenergic Receptors (Adrenoceptors): Classification

Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic...
Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
Glomerular Filtration Rate and its Regulation01:28

Glomerular Filtration Rate and its Regulation

The Glomerular Filtration Rate (GFR) is a measure of kidney function, reflecting the volume of filtrate formed per minute in the kidneys. On average, GFR is approximately 125 mL/min in males and 105 mL/min in females. Maintaining a relatively constant GFR is essential for the kidneys to effectively regulate body fluid homeostasis and maintain extracellular stability.
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...