Int J Clin Exp Med. 2015 Oct 15;8(10):18327-34. eCollection 2015.
Gingipains from Porphyromonas gingivalis promote the transformation and proliferation of vascular smooth muscle cell phenotypes.
International journal of clinical and experimental medicine
Chong Cao, Xiaowei Ji, Xin Luo, Liangjun Zhong
Affiliations
Affiliations
- Department of Periodontology, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
- Department of Prosthodontics, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
- Department of Pharmacology, The Basic Medical Sciences College of Xinjiang Medical University Urumqi 830054, China.
- Department of Periodontology, The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054, China; Medical College of Hangzhou Normal UniversityHangzhou 311121, China; Department of Stomatology, The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310015, China.
PMID: 26770435
PMCID: PMC4694335
Abstract
The aim of the present study was to ascertain the effect of Porphyromonas gingivalis cysteine protease gingipain on the proliferation of rat aortic smooth muscle cells (RASMCs). Gingipains were isolated and purified from the supernatant of P. gingivalis W83, which was cultured under standard anaerobic conditions; primary RASMCs were also cultured. RASMCs were exposed to 200, 100, 50, 25, 12, 6, 3, 1, and 0 μg/mL activated gingipains and the proliferation was evaluated using a cell counting kit-8 (CCK-8) assay after 48 h. α-Smooth muscle actin (α-SMA) and osteopontin (OPN) expression were measured by immunohistochemical staining. In addition, RASMCs were stimulated with 5, 10, 20, and 40 μM KYT-1 (arg-gingipain inhibitor) and KYT-36 (lys-gingipain inhibitor) in combination with the gingipain extracts. Different concentrations of gingipains significantly promoted the proliferation of RASMCs, except those treated with 1 μg/mL, compared to the untreated controls. The proliferation was sustained at a concentration above 12 μg/mL. Immunohistochemical staining showed OPN expression after gingipain stimulation. The proliferative effects of gingipains on RASMCs were blocked after treatment with 10 μM KYT-1 or 10 μM KYT-36 (P < 0.0001); however, the difference between KYT-1 and KYT-36 groups was not statistically significant. These results demonstrated that gingipains can promote phenotypic transformation and proliferation of RASMCs and their effects were blocked by KYT-1 and KYT-36, which help us to ascertain whether Rgp or Kgp contributes to the development of atherosclerosis.
Keywords: Gingipains; phenotype transformation; proliferation; smooth muscle cell
References
- Oral Microbiol Immunol. 2005 Oct;20(5):296-302 - PubMed
- FEBS Lett. 2009 Jan 5;583(1):128-34 - PubMed
- Arch Med Res. 2015 Feb;46(2):112-7 - PubMed
- Physiology (Bethesda). 2009 Feb;24:36-44 - PubMed
- J Biochem. 2006 Nov;140(5):713-23 - PubMed
- Int J Mol Med. 2014 May;33(5):1341-7 - PubMed
- Future Microbiol. 2009 May;4(4):471-87 - PubMed
- Immunopharmacol Immunotoxicol. 2012 Jun;34(3):470-6 - PubMed
- J Periodontol. 2011 Nov;82(11):1616-22 - PubMed
- Curr Protein Pept Sci. 2003 Dec;4(6):409-26 - PubMed
- Atherosclerosis. 2014 Oct;236(2):327-37 - PubMed
- Toxins (Basel). 2010 Mar;2(3):341-52 - PubMed
- Mol Pharmacol. 2004 Dec;66(6):1599-606 - PubMed
- Mol Cell Biochem. 2013 May;377(1-2):1-10 - PubMed
- BMC Genomics. 2013 Nov 09;14:770 - PubMed
- Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2370-7 - PubMed
- Cell Microbiol. 2012 Jul;14(7):1085-96 - PubMed
- PLoS One. 2014 May 16;9(5):e97811 - PubMed
- J Pharmacol Sci. 2010;113(2):115-9 - PubMed
- J Clin Periodontol. 2013 Oct;40(10):924-32 - PubMed
- Physiol Rev. 2004 Jul;84(3):767-801 - PubMed
- Infect Immun. 2005 Mar;73(3):1543-52 - PubMed
- Crit Rev Oral Biol Med. 2004 Nov 01;15(6):403-13 - PubMed
- Arch Oral Biol. 2011 Dec;56(12):1583-91 - PubMed
- J Clin Invest. 1994 Jun;93(6):2393-402 - PubMed
- Int J Mol Sci. 2014 Oct 17;15(10):18747-61 - PubMed
- J Periodontal Res. 2011 Dec;46(6):749-55 - PubMed
Publication Types