Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases

Toshihiro Tsuruda, Guido Boerrigter, Brenda K. Huntley, Josh A. Noser, Alessandro Cataliotti, Lisa C. Costello-Boerrigter, Horng Haur Chen, John C Jr. Burnett

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

Cardiac fibroblasts (CFs) produce extracellular matrix proteins and participate in the remodeling of the heart. It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix turnover. In this study, we examined the production of BNP in adult canine CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs). BNP mRNA was detected in CFs, and a specific radioimmunoassay demonstrated that BNP1-32 was secreted into the media at a rate of 11.2±1.0 pg/105 cells per 48 hours (mean±SEM). The amount of BNP secretion was significantly (P<0.01) augmented by 10-7 mol/L tumor necrosis factor-α in a time-dependent manner. BNP significantly (P<0.01) inhibited de novo collagen synthesis as assessed by [3H]proline incorporation, whereas zymographic MMP-2 (gelatinase) abundance was significantly (P<0.05) stimulated by BNP between 10-7 and 10-66 mol/L. In addition, protein expression of MMP-1, -2, and -3 and membranous type-1 MMP was significantly increased by 10-6 mol/L BNP. The cGMP analogue 8-bromo-cGMP (10-4 mol/L) mimicked the BNP effect, whereas inhibition of protein kinase G by KT5823 (10-6 mol/L) significantly (P<0.05) attenuated BNP-induced zymographic MMP-2 abundance. In summary, this study reports that BNP is present in cultured CFs and that BNP decreases collagen synthesis and increases MMPs via cGMP-protein kinase G signaling. These in vitro findings support a role for BNP as a regulator of myocardial structure via control of cardiac fibroblast function.

Original languageEnglish (US)
Pages (from-to)1127-1134
Number of pages8
JournalCirculation Research
Volume91
Issue number12
DOIs
StatePublished - Dec 2002

Fingerprint

Brain Natriuretic Peptide
Matrix Metalloproteinases
Fibroblasts
Matrix Metalloproteinase 2
Cyclic GMP-Dependent Protein Kinases
Matrix Metalloproteinase 1
Collagen
Natriuretic Agents
Gelatinases
Extracellular Matrix Proteins
Proline
Radioimmunoassay
Extracellular Matrix
Canidae

Keywords

  • Cardiac fibroblasts
  • CGMP
  • Extracellular matrix
  • Protein kinase G
  • Remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tsuruda, T., Boerrigter, G., Huntley, B. K., Noser, J. A., Cataliotti, A., Costello-Boerrigter, L. C., ... Burnett, J. C. J. (2002). Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. Circulation Research, 91(12), 1127-1134. https://doi.org/10.1161/01.RES.0000046234.73401.70

Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. / Tsuruda, Toshihiro; Boerrigter, Guido; Huntley, Brenda K.; Noser, Josh A.; Cataliotti, Alessandro; Costello-Boerrigter, Lisa C.; Chen, Horng Haur; Burnett, John C Jr.

In: Circulation Research, Vol. 91, No. 12, 12.2002, p. 1127-1134.

Research output: Contribution to journalArticle

Tsuruda, T, Boerrigter, G, Huntley, BK, Noser, JA, Cataliotti, A, Costello-Boerrigter, LC, Chen, HH & Burnett, JCJ 2002, 'Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases', Circulation Research, vol. 91, no. 12, pp. 1127-1134. https://doi.org/10.1161/01.RES.0000046234.73401.70
Tsuruda T, Boerrigter G, Huntley BK, Noser JA, Cataliotti A, Costello-Boerrigter LC et al. Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. Circulation Research. 2002 Dec;91(12):1127-1134. https://doi.org/10.1161/01.RES.0000046234.73401.70
Tsuruda, Toshihiro ; Boerrigter, Guido ; Huntley, Brenda K. ; Noser, Josh A. ; Cataliotti, Alessandro ; Costello-Boerrigter, Lisa C. ; Chen, Horng Haur ; Burnett, John C Jr. / Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. In: Circulation Research. 2002 ; Vol. 91, No. 12. pp. 1127-1134.
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abstract = "Cardiac fibroblasts (CFs) produce extracellular matrix proteins and participate in the remodeling of the heart. It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix turnover. In this study, we examined the production of BNP in adult canine CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs). BNP mRNA was detected in CFs, and a specific radioimmunoassay demonstrated that BNP1-32 was secreted into the media at a rate of 11.2±1.0 pg/105 cells per 48 hours (mean±SEM). The amount of BNP secretion was significantly (P<0.01) augmented by 10-7 mol/L tumor necrosis factor-α in a time-dependent manner. BNP significantly (P<0.01) inhibited de novo collagen synthesis as assessed by [3H]proline incorporation, whereas zymographic MMP-2 (gelatinase) abundance was significantly (P<0.05) stimulated by BNP between 10-7 and 10-66 mol/L. In addition, protein expression of MMP-1, -2, and -3 and membranous type-1 MMP was significantly increased by 10-6 mol/L BNP. The cGMP analogue 8-bromo-cGMP (10-4 mol/L) mimicked the BNP effect, whereas inhibition of protein kinase G by KT5823 (10-6 mol/L) significantly (P<0.05) attenuated BNP-induced zymographic MMP-2 abundance. In summary, this study reports that BNP is present in cultured CFs and that BNP decreases collagen synthesis and increases MMPs via cGMP-protein kinase G signaling. These in vitro findings support a role for BNP as a regulator of myocardial structure via control of cardiac fibroblast function.",
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AU - Cataliotti, Alessandro

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