title: Cross talk between MMP2-Spm-Cer-S1P and ERK1/2 in proliferation of pulmonary artery smooth muscle cells under angiotensin II stimulation.
abstract: The aim of the present study is to establish the mechanism associated with the proliferation of PASMCs under ANG II stimulation. The results showed that treatment of PASMCs with ANG II induces an increase in cell proliferation and 100 nM was the optimum concentration for maximum increase in proliferation of the cells. Pretreatment of the cells with AT1, but not AT2, receptor antagonist inhibited ANG II induced cell proliferation. Pretreatment with pharmacological and genetic inhibitors of sphingomyelinase (SMase) and sphingosine kinase (SPHK) prevented ANG II-induced cell proliferation. ANG II has also been shown to induce SMase activity, SPHK phosphorylation and S1P production. In addition, ANG II caused an increase in proMMP-2 expression and activation, ERK1/2 phosphorylation and NADPH oxidase activation. Upon inhibition of MMP-2, SMase activity and S1P level were curbed leading to inhibition of cell proliferation. SPHK was phosphorylated by ERK1/2 during ET-1 stimulation of the cells. ANG II-induced ERK1/2 phosphorylation and proMMP-2 expression and activation in the cells were abrogated upon inhibition of NADPH oxidase activity. Overall, NADPH oxidase plays an important role in proMMP-2 expression and activation and that MMP-2 mediated SMC proliferation occurs through the involvement of Spm-Cer-S1P signaling axis under ANG II stimulation of PASMCs.
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India.
authors.forename: Animesh
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India.
authors.forename: Jaganmay
authors.initials: J
authors.lastname: Sarkar
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India.
authors.forename: Pijush Kanti
authors.initials: PK
authors.lastname: Pramanik
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India.
authors.forename: Tapati
authors.initials: T
authors.lastname: Chakraborti
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India. Electronic address: sajal_chakraborti@yahoo.com.
authors.forename: Sajal
authors.initials: S
authors.lastname: Chakraborti
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D002518:Ceramides / Q000737:chemistry*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D043484:Proprotein Convertases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D034741:RNA, Small Interfering / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D014162:Transfection
chemical_list: D002518:Ceramides; D034741:RNA, Small Interfering; D013109:Sphingomyelins; D000804:Angiotensin II; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D013108:Sphingomyelin Phosphodiesterase; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1; D020778:Matrix Metalloproteinase 2; D010100:Oxygen
keywords: ANG II; BPASMC; Cell proliferation; NADPH oxidase; S1P; proMMP-2