Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors

Ryoko Shimizu, H. Sasamura, M. Mifune, H. Nakaya, M. Kuroda, M. Hayashi, T. Saruta

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Recent studies have shown that proteoglycans play an important role in the development of vascular disease and renal failure. In this study, the effects of angiotensin II (AngII) type 1 (AT1) and type 2 (AT2) receptor stimulation on glycosaminoglycan and proteoglycan core protein synthesis in vascular smooth muscle cells (VSMC) were examined. Treatment of ATI receptor-expressing VSMC with AngII resulted in a dose-dependent and time-dependent increase (2- to 4-fold) in 3H-glucosamine/35S-sulfate incorporation, which was abolished by pretreatment with the AT1 receptor antagonist, losartan. The effects of AngII were inhibited by the epidermal growth factor receptor inhibitor, AG1478, and the mitagen-activated protein kinase kinase inhibitor, PD98059, but not the protein kinase C inhibitors, chelerythrine and staurosporine. AngII treatment also resulted in significant increases in the mRNA of the core proteins, versican, biglycan, and perlecan. The effects of AT2 receptor stimulation were examined by retroviral transfection of VSMC with the AT2 receptor. Stimulation of the AT2 receptor in these VSMC-AT2 cells resulted in a significant (1.3-fold) increase in proteoglycan synthesis, which was abolished by the AT2 receptor antagonist, PD123319, and attenuated by pretreatment with pertussis toxin. These results implicate both AT1 and AT2 receptors in the regulation of proteoglycan synthesis and suggest the involvement of epidermal growth factor receptor-dependent tyrosine kinase pathways and Gai/o-mediated mechanisms in the effects of the two receptors.

Original languageEnglish
Pages (from-to)2609-2615
Number of pages7
JournalJournal of the American Society of Nephrology
Volume12
Issue number12
Publication statusPublished - 2001

Fingerprint

Angiotensin Type 1 Receptor
Proteoglycans
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Angiotensin II
Epidermal Growth Factor Receptor
Versicans
Biglycan
Staurosporine
Losartan
Protein C Inhibitor
Glucosamine
Pertussis Toxin
Protein Kinase Inhibitors
Glycosaminoglycans
Vascular Diseases
Protein-Tyrosine Kinases
Protein Kinases
Protein Kinase C

ASJC Scopus subject areas

  • Nephrology

Cite this

Shimizu, R., Sasamura, H., Mifune, M., Nakaya, H., Kuroda, M., Hayashi, M., & Saruta, T. (2001). Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. Journal of the American Society of Nephrology, 12(12), 2609-2615.

Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. / Shimizu, Ryoko; Sasamura, H.; Mifune, M.; Nakaya, H.; Kuroda, M.; Hayashi, M.; Saruta, T.

In: Journal of the American Society of Nephrology, Vol. 12, No. 12, 2001, p. 2609-2615.

Research output: Contribution to journalArticle

Shimizu, R, Sasamura, H, Mifune, M, Nakaya, H, Kuroda, M, Hayashi, M & Saruta, T 2001, 'Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors', Journal of the American Society of Nephrology, vol. 12, no. 12, pp. 2609-2615.
Shimizu, Ryoko ; Sasamura, H. ; Mifune, M. ; Nakaya, H. ; Kuroda, M. ; Hayashi, M. ; Saruta, T. / Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. In: Journal of the American Society of Nephrology. 2001 ; Vol. 12, No. 12. pp. 2609-2615.
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