{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lindsey ML"],"funding":["BLRD VA","NHLBI NIH HHS","NIGMS NIH HHS","PHS HHS"],"pagination":["879-86"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4764993"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["93(10)"],"pubmed_abstract":["Osteopontin is robustly upregulated following myocardial infarction (MI), which suggests that it has an important role in post-MI remodeling of the left ventricle (LV). Osteopontin deletion results in increased LV dilation and worsened cardiac function. Thus, osteopontin exerts protective effects post-MI, but the mechanisms have yet to be defined. Matrix metalloproteinases (MMPs) regulate LV remodeling post-MI, and osteopontin is a known substrate for MMP-2, -3, -7, and -9, although the cleavage sites have not been mapped. Osteopontin-derived peptides can exert distinct biological functions that may depend on their cleavage sites. We mapped the MMP-9 cleavage sites via LC-MS/MS analysis using label-free and N-terminal labeling methods, and compared them with those of MMP-2, -3, and -7. Each MMP yielded a unique cleavage profile with few overlapping cleavage sites. Using synthetic peptides, we validated 3 sites for MMP-9 cleavage at amino acid positions 151-152, 193-194, and 195-196. Four peptides were synthesized based on the upstream- and downstream-generated fragments and were tested for biological activity in isolated cardiac fibroblasts. Two peptides increased cardiac fibroblast migration rates post-wounding (p < 0.05 compared with the negative control). Our study highlights the importance of osteopontin processing, and confirms that different cleavage sites generate osteopontin peptides with distinct biological functions."],"journal":["Canadian journal of physiology and pharmacology"],"pubmed_title":["Osteopontin is proteolytically processed by matrix metalloproteinase 9."],"pmcid":["PMC4764993"],"funding_grant_id":["P01 HL051971","R01HL075360","R01 HL095852","HL051971","P20GM104357","HHSN268201000036C","P20 GM104357","N01-HV-00244","R01 HL075360","I01 BX000505","268201000036C","HL095852"],"pubmed_authors":["Padmanabhan Iyer R","Tian Y","Lindsey ML","de Castro Bras LE","Zouein FA"],"additional_accession":[]},"is_claimable":false,"name":"Osteopontin is proteolytically processed by matrix metalloproteinase 9.","description":"Osteopontin is robustly upregulated following myocardial infarction (MI), which suggests that it has an important role in post-MI remodeling of the left ventricle (LV). Osteopontin deletion results in increased LV dilation and worsened cardiac function. Thus, osteopontin exerts protective effects post-MI, but the mechanisms have yet to be defined. Matrix metalloproteinases (MMPs) regulate LV remodeling post-MI, and osteopontin is a known substrate for MMP-2, -3, -7, and -9, although the cleavage sites have not been mapped. Osteopontin-derived peptides can exert distinct biological functions that may depend on their cleavage sites. We mapped the MMP-9 cleavage sites via LC-MS/MS analysis using label-free and N-terminal labeling methods, and compared them with those of MMP-2, -3, and -7. Each MMP yielded a unique cleavage profile with few overlapping cleavage sites. Using synthetic peptides, we validated 3 sites for MMP-9 cleavage at amino acid positions 151-152, 193-194, and 195-196. Four peptides were synthesized based on the upstream- and downstream-generated fragments and were tested for biological activity in isolated cardiac fibroblasts. Two peptides increased cardiac fibroblast migration rates post-wounding (p < 0.05 compared with the negative control). Our study highlights the importance of osteopontin processing, and confirms that different cleavage sites generate osteopontin peptides with distinct biological functions.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Oct","modification":"2020-11-19T14:39:11Z","creation":"2019-03-27T02:09:45Z"},"accession":"S-EPMC4764993","cross_references":{"pubmed":["26176332"],"doi":["10.1139/cjpp-2015-0019"]}}