| http://purl.uniprot.org/citations/22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22440257 | http://www.w3.org/2000/01/rdf-schema#comment | "Uncontrolled increases of matrix metalloproteinase-9 (MMP-9) activity have been causally linked to epithelial barrier disruption and severe symptoms of inflammatory diseases such as dry eye (DE). The data presented here show that the anti-inflammatory, cytoprotective intracellular and extracellular chaperone protein clusterin (CLU) interacts with MMP-9 both inside and outside epithelial cells. CLU bound very strongly to active MMP-9, with an affinity constant K(D) of 2.63 nmol/L. Unexpectedly, CLU had a much higher affinity for pro-MMP-9 than for active MMP-9 or pro-MMP-2, requiring the N-terminal propeptide domain of pro-MMP-9. The significance of the interaction between CLU and MMP-9 was demonstrated by the observation that CLU prevents stress-induced MMP-9 aggregation and inhibits MMP-9 enzymatic activity. Furthermore, CLU inhibited MMP-9-mediated disintegration of the tight junction structure formed between human epithelial cells. Additionally, CLU inhibited enzymatic activities of MMP-2, MMP-3, and MMP-7. Treatment with proinflammatory cytokines, which are known to increase MMP-9 transcription under inflammatory conditions, reduced the expression of CLU in human epithelial cells. Similarly, in a mouse model of human DE, inflammatory stress depleted CLU in the ocular surface epithelium but allowed MMP-9 to prevail therein. The present results thus provide novel insights into previously unrecognized mechanisms by which CLU maintains fluid-epithelial interface homeostasis, thereby preventing the onset of inflammatory conditions, especially where MMP-9 is actively involved."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajpath.2012.01.025"xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Martin A."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Patel N."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Jeong S."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Itakura T."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Fini M.E."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Ledee D.R."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/author | "Gordon G.M."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/pages | "2028-2039"xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/title | "Interaction of clusterin and matrix metalloproteinase-9 and its implication for epithelial homeostasis and inflammation."xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://purl.uniprot.org/core/volume | "180"xsd:string |
| http://purl.uniprot.org/citations/22440257 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22440257 |
| http://purl.uniprot.org/citations/22440257 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22440257 |
| http://purl.uniprot.org/uniprot/#_E9Q8Y5-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_E9Q9B8-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_A2A5K8-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_E9Q2G2-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_E9PXG5-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_D6RFP9-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_E9PUU2-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |
| http://purl.uniprot.org/uniprot/#_P41245-mappedCitation-22440257 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22440257 |