Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 2001 Jul 15;357(Pt 2):587–592. doi: 10.1042/0264-6021:3570587

G-protein-coupled-receptor activation of the smooth muscle calponin gene.

N O Dulin 1, S N Orlov 1, C M Kitchen 1, T A Voyno-Yasenetskaya 1, J M Miano 1
PMCID: PMC1221990  PMID: 11439113

Abstract

A hallmark of cultured smooth muscle cells (SMCs) is the rapid down-regulation of several lineage-restricted genes that define their in vivo differentiated phenotype. Identifying factors that maintain an SMC differentiated phenotype has important implications in understanding the molecular underpinnings governing SMC differentiation and their subversion to an altered phenotype in various disease settings. Here, we show that several G-protein coupled receptors [alpha-thrombin, lysophosphatidic acid and angiotensin II (AII)] increase the expression of smooth muscle calponin (SM-Calp) in rat and human SMC. The increase in SM-Calp protein appears to be selective for G-protein-coupled receptors as epidermal growth factor was without effect. Studies using AII showed a 30-fold increase in SM-Calp protein, which was dose- and time-dependent and mediated by the angiotensin receptor-1 (AT1 receptor). The increase in SM-Calp protein with AII was attributable to transcriptional activation of SM-Calp based on increases in steady-state SM-Calp mRNA, increases in SM-Calp promoter activity and complete abrogation of protein induction with actinomycin D. To examine the potential role of extracellular signal-regulated kinase (Erk1/2), protein kinase B, p38 mitogen-activated protein kinase and protein kinase C in AII-induced SM-Calp, inhibitors to each of the signalling pathways were used. None of these signalling molecules appears to be crucial for AII-induced SM-Calp expression, although Erk1/2 may be partially involved. These results identify SM-Calp as a target of AII-mediated signalling, and suggest that the SMC response to AII may incorporate a novel activity of SM-Calp.

Full Text

The Full Text of this article is available as a PDF (211.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aikawa M., Sivam P. N., Kuro-o M., Kimura K., Nakahara K., Takewaki S., Ueda M., Yamaguchi H., Yazaki Y., Periasamy M. Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis. Circ Res. 1993 Dec;73(6):1000–1012. doi: 10.1161/01.res.73.6.1000. [DOI] [PubMed] [Google Scholar]
  2. Barja F., Coughlin C., Belin D., Gabbiani G. Actin isoform synthesis and mRNA levels in quiescent and proliferating rat aortic smooth muscle cells in vivo and in vitro. Lab Invest. 1986 Aug;55(2):226–233. [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Devlin A. M., Gordon J. F., Davidson A. O., Clark J. S., Hamilton C. A., Morton J. J., Campbell A. M., Reid J. L., Dominiczak A. F. The effects of perindopril on vascular smooth muscle polyploidy in stroke-prone spontaneously hypertensive rats. J Hypertens. 1995 Feb;13(2):211–218. [PubMed] [Google Scholar]
  5. Firulli A. B., Han D., Kelly-Roloff L., Koteliansky V. E., Schwartz S. M., Olson E. N., Miano J. M. A comparative molecular analysis of four rat smooth muscle cell lines. In Vitro Cell Dev Biol Anim. 1998 Mar;34(3):217–226. doi: 10.1007/s11626-998-0127-5. [DOI] [PubMed] [Google Scholar]
  6. Gimona M., Herzog M., Vandekerckhove J., Small J. V. Smooth muscle specific expression of calponin. FEBS Lett. 1990 Nov 12;274(1-2):159–162. doi: 10.1016/0014-5793(90)81353-p. [DOI] [PubMed] [Google Scholar]
  7. Hautmann M. B., Madsen C. S., Owens G. K. A transforming growth factor beta (TGFbeta) control element drives TGFbeta-induced stimulation of smooth muscle alpha-actin gene expression in concert with two CArG elements. J Biol Chem. 1997 Apr 18;272(16):10948–10956. doi: 10.1074/jbc.272.16.10948. [DOI] [PubMed] [Google Scholar]
  8. Hautmann M. B., Thompson M. M., Swartz E. A., Olson E. N., Owens G. K. Angiotensin II-induced stimulation of smooth muscle alpha-actin expression by serum response factor and the homeodomain transcription factor MHox. Circ Res. 1997 Oct;81(4):600–610. doi: 10.1161/01.res.81.4.600. [DOI] [PubMed] [Google Scholar]
  9. Horiuchi A., Nikaido T., Taniguchi S., Fujii S. Possible role of calponin h1 as a tumor suppressor in human uterine leiomyosarcoma. J Natl Cancer Inst. 1999 May 5;91(9):790–796. doi: 10.1093/jnci/91.9.790. [DOI] [PubMed] [Google Scholar]
  10. Hutchinson H. G., Hein L., Fujinaga M., Pratt R. E. Modulation of vascular development and injury by angiotensin II. Cardiovasc Res. 1999 Mar;41(3):689–700. doi: 10.1016/s0008-6363(98)00267-3. [DOI] [PubMed] [Google Scholar]
  11. Jiang Z., Grange R. W., Walsh M. P., Kamm K. E. Adenovirus-mediated transfer of the smooth muscle cell calponin gene inhibits proliferation of smooth muscle cells and fibroblasts. FEBS Lett. 1997 Aug 25;413(3):441–445. doi: 10.1016/s0014-5793(97)00944-7. [DOI] [PubMed] [Google Scholar]
  12. Kitami Y., Maguchi M., Nishida W., Okura T., Kohara K., Hiwada K. The unique 5-flanking region of the human basic calponin gene. Hypertens Res. 1999 Sep;22(3):187–193. doi: 10.1291/hypres.22.187. [DOI] [PubMed] [Google Scholar]
  13. Leinweber B. D., Leavis P. C., Grabarek Z., Wang C. L., Morgan K. G. Extracellular regulated kinase (ERK) interaction with actin and the calponin homology (CH) domain of actin-binding proteins. Biochem J. 1999 Nov 15;344(Pt 1):117–123. [PMC free article] [PubMed] [Google Scholar]
  14. Mabuchi K., Li Y., Tao T., Wang C. L. Immunocytochemical localization of caldesmon and calponin in chicken gizzard smooth muscle. J Muscle Res Cell Motil. 1996 Apr;17(2):243–260. doi: 10.1007/BF00124246. [DOI] [PubMed] [Google Scholar]
  15. Matthew J. D., Khromov A. S., McDuffie M. J., Somlyo A. V., Somlyo A. P., Taniguchi S., Takahashi K. Contractile properties and proteins of smooth muscles of a calponin knockout mouse. J Physiol. 2000 Dec 15;529(Pt 3):811–824. doi: 10.1111/j.1469-7793.2000.00811.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miano J. M., Carlson M. J., Spencer J. A., Misra R. P. Serum response factor-dependent regulation of the smooth muscle calponin gene. J Biol Chem. 2000 Mar 31;275(13):9814–9822. doi: 10.1074/jbc.275.13.9814. [DOI] [PubMed] [Google Scholar]
  17. Miano J. M., Cserjesi P., Ligon K. L., Periasamy M., Olson E. N. Smooth muscle myosin heavy chain exclusively marks the smooth muscle lineage during mouse embryogenesis. Circ Res. 1994 Nov;75(5):803–812. doi: 10.1161/01.res.75.5.803. [DOI] [PubMed] [Google Scholar]
  18. Miano J. M., Krahe R., Garcia E., Elliott J. M., Olson E. N. Expression, genomic structure and high resolution mapping to 19p13.2 of the human smooth muscle cell calponin gene. Gene. 1997 Sep 15;197(1-2):215–224. doi: 10.1016/s0378-1119(97)00265-5. [DOI] [PubMed] [Google Scholar]
  19. Miano J. M., Olson E. N. Expression of the smooth muscle cell calponin gene marks the early cardiac and smooth muscle cell lineages during mouse embryogenesis. J Biol Chem. 1996 Mar 22;271(12):7095–7103. doi: 10.1074/jbc.271.12.7095. [DOI] [PubMed] [Google Scholar]
  20. North A. J., Gimona M., Cross R. A., Small J. V. Calponin is localised in both the contractile apparatus and the cytoskeleton of smooth muscle cells. J Cell Sci. 1994 Mar;107(Pt 3):437–444. doi: 10.1242/jcs.107.3.437. [DOI] [PubMed] [Google Scholar]
  21. Owens G. K. Regulation of differentiation of vascular smooth muscle cells. Physiol Rev. 1995 Jul;75(3):487–517. doi: 10.1152/physrev.1995.75.3.487. [DOI] [PubMed] [Google Scholar]
  22. Parker C. A., Takahashi K., Tao T., Morgan K. G. Agonist-induced redistribution of calponin in contractile vascular smooth muscle cells. Am J Physiol. 1994 Nov;267(5 Pt 1):C1262–C1270. doi: 10.1152/ajpcell.1994.267.5.C1262. [DOI] [PubMed] [Google Scholar]
  23. Rovner A. S., Murphy R. A., Owens G. K. Expression of smooth muscle and nonmuscle myosin heavy chains in cultured vascular smooth muscle cells. J Biol Chem. 1986 Nov 5;261(31):14740–14745. [PubMed] [Google Scholar]
  24. Samaha F. F., Ip H. S., Morrisey E. E., Seltzer J., Tang Z., Solway J., Parmacek M. S. Developmental pattern of expression and genomic organization of the calponin-h1 gene. A contractile smooth muscle cell marker. J Biol Chem. 1996 Jan 5;271(1):395–403. doi: 10.1074/jbc.271.1.395. [DOI] [PubMed] [Google Scholar]
  25. Yamada H., Akishita M., Ito M., Tamura K., Daviet L., Lehtonen J. Y., Dzau V. J., Horiuchi M. AT2 receptor and vascular smooth muscle cell differentiation in vascular development. Hypertension. 1999 Jun;33(6):1414–1419. doi: 10.1161/01.hyp.33.6.1414. [DOI] [PubMed] [Google Scholar]
  26. Yoshikawa H., Taniguchi S. I., Yamamura H., Mori S., Sugimoto M., Miyado K., Nakamura K., Nakao K., Katsuki M., Shibata N. Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses. Genes Cells. 1998 Oct;3(10):685–695. doi: 10.1046/j.1365-2443.1998.00214.x. [DOI] [PubMed] [Google Scholar]
  27. di Gioia C. R., van de Greef W. M., Sperti G., Castoldi G., Todaro N., Ierardi C., Pieruzzi F., Stella A. Angiotensin II increases calponin expression in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun. 2000 Dec 29;279(3):965–969. doi: 10.1006/bbrc.2000.4049. [DOI] [PubMed] [Google Scholar]
  28. van der Loop F. T., Schaart G., Timmer E. D., Ramaekers F. C., van Eys G. J. Smoothelin, a novel cytoskeletal protein specific for smooth muscle cells. J Cell Biol. 1996 Jul;134(2):401–411. doi: 10.1083/jcb.134.2.401. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES