Faculty Collaboration Database

Non-human primate and rat cardiac fibroblasts show similar extracellular matrix-related and cellular adhesion gene responses to substance P. Heart Lung Circ 2015 Apr;24(4):395-403

Date

01/01/2015

Pubmed ID

25550118

Pubmed Central ID

PMC4492475

DOI

10.1016/j.hlc.2014.11.015

Scopus ID

2-s2.0-84925035946 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

BACKGROUND: The sensory nerve neuropeptide substance P (SP) regulates cardiac fibrosis in rodents under pressure overload conditions. Interestingly, SP induces transient increased expression of specific genes in isolated rat cardiac fibroblasts, without resultant changes in cell function. This suggests that SP 'primes' fibroblasts, but does not directly activate them. We investigated whether these unusual findings are specific to rodent fibroblasts or are translatable to a larger animal model more closely related to humans.

METHODS: We compared the effects of SP on genes associated with extracellular matrix (ECM) regulation, cell-cell adhesion, cell-matrix adhesion and ECM in cardiac fibroblasts isolated from a non-human primate and Sprague-Dawley rats.

RESULTS: We found that rodent and non-human primate cardiac fibroblasts showed similar responses in genes that relate to ECM regulation and cell adhesion in response to SP. There were large discrepancies in ECM component genes, however, this did not result in collagen or laminin synthesis in rat or non-human primate fibroblasts in response to SP.

CONCLUSIONS: This study further supports the notion that SP serves as a 'primer' for fibroblasts rather than initiating direct effects and suggests that rodent fibroblasts are a suitable model for studying gene and functional responses to SP in the absence of human or non-human primate fibroblasts.

Author List

Meléndez GC, Manteufel EJ, Dehlin HM, Register TC, Levick SP

MESH terms used to index this publication - Major topics in bold

Animals
Cell Adhesion
Extracellular Matrix
Female
Fibroblasts
Gene Expression Regulation
Humans
Macaca fascicularis
Male
Myocardium
Rats
Rats, Sprague-Dawley
Substance P