NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF

PLoS One. 2016 Feb 10;11(2):e0149031. doi: 10.1371/journal.pone.0149031. eCollection 2016.

Abstract

It is well known that natriuretic peptides (NPs) are involved in the regulation of gastrointestinal motility. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal motility and gastrointestinal dyskinesia is one of the important digestive tract symptoms of depression. However, it is unclear whether they are involved in depression-induced loss of ICC. The aim of the present study was to investigate the relationship between the natriuretic peptide signaling pathway and depression-induced loss of gastric ICC in depressed rats. These results showed that the expression of c-kit and stem cell factor (SCF) in smooth muscle layers of stomach were down-regulated in depressed rats at the mRNA and protein levels. The expression of natriuretic peptide receptor (NPR)-A, B and C were up-regulated in the stomach of depressed rats at the mRNA and protein levels. NPR-A, B and C can significantly decrease the expression of SCF to treat cultured gastric smooth muscle cells (GSMCs) obtained from normal rats with different concentrations of C-type natriuretic peptide (CNP). Pretreatment of cultured GSMCs with 8-Brom-cGMP (8-Br-cGMP, a membrane permeable cGMP analog), cANF (a specific NPR-C agonist) and CNP (10-6 mol/L) demonstrated that 8-Br-cGMP had a similar effect as CNP, but treatment with cANF did not. The results of the methyl thiazolyl tetrazolium bromide (MTT) assay indicated that high concentrations of cANF (10-6 mol/L) restrained the proliferation of cultured GSMCs. Taken together, these results indicate that the up-regulation of the NPs/NPR-C and NPs/NPR-A, B/cGMP signaling pathways may be involved in depression-induced loss of gastric ICC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Cell Proliferation
  • Depression / metabolism*
  • Depression / physiopathology
  • Down-Regulation
  • Gastric Mucosa / metabolism*
  • Gene Expression Regulation
  • Interstitial Cells of Cajal / metabolism*
  • Male
  • Myocytes, Smooth Muscle / cytology
  • Natriuretic Peptides / metabolism
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Atrial Natriuretic Factor / biosynthesis
  • Receptors, Atrial Natriuretic Factor / metabolism
  • Signal Transduction*
  • Stem Cell Factor / biosynthesis
  • Stem Cell Factor / metabolism*
  • Tetrazolium Salts / chemistry
  • Thiazoles / chemistry
  • Up-Regulation

Substances

  • Natriuretic Peptides
  • Stem Cell Factor
  • Tetrazolium Salts
  • Thiazoles
  • Proto-Oncogene Proteins c-kit
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor A
  • atrial natriuretic factor receptor B
  • atrial natriuretic factor receptor C
  • thiazolyl blue

Grants and funding

The work was supported by the following: National Basic Research Program of China (973 Program), No. 2013CB531703, HSG; The National Natural Science Foundation of China, No. 81273919, HSG; and Natural Science Foundation of Liaoning Province, No. 2012225020 and No. 2013023002, HSG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.