title: The matri-cellular proteins 'cysteine-rich, angiogenic-inducer, 61' and 'connective tissue growth factor' are regulated in experimentally-induced sepsis with multiple organ dysfunction.
abstract: Organ failure is a severe complication in sepsis for which the pathophysiology remains incompletely understood. Recently, the matri-cellular cysteine-rich, angiogenic induced, 61 (Cyr61/CCN1); connective tissue growth factor (Ctgf/CCN2); and nephroblastoma overexpressed gene (Nov/CCN3) (CCN)-protein family have been attributed organ-protective properties. Their expression is sensitive to mediators of sepsis pathophysiology but a potential role in sepsis remains elusive. To provide an initial assessment, 50 rats were subjected to 18 h of cecal-ligation and puncture or sham operation. Hepatic and pulmonary CCN1 mRNA displayed an average 7.4- and 3.3-fold induction, while its cardiac expression was unchanged. The changes coincided with excessive hepatic and pulmonary inflammatory gene activation and a restricted cardiac inflammation. Furthermore, hepatocytes displayed a dosage-dependent CCN1 mRNA response in vitro, supporting a cytokine-mediated CCN1 regulation in sepsis. CCN2 mRNA was 2.2-fold induced in the liver, while 2.0-fold and 1.4-fold repressed in the heart and lung. Meanwhile, it did not respond to TNF-α exposure in vitro, which indicates different means of regulation than for CCN1. Taken together, this study provides the first evidence for multi-organ regulation of CCN1 and CCN2 in early stages of sepsis, and implies the eruption of inflammatory mediators as a potential mechanism behind the observed CCN1 regulation.
authors.affiliation: Institute for Surgical Research, Oslo University Hospital HF, Oslo, Norway. claus.vinter@rr-research.no
authors.forename: Claus V B
authors.initials: CV
authors.lastname: Hviid
authors.forename: Johanna Samulin
authors.initials: JS
authors.lastname: Erdem
authors.forename: David
authors.initials: D
authors.lastname: Kunke
authors.forename: Shakil M
authors.initials: SM
authors.lastname: Ahmed
authors.forename: Signe F
authors.initials: SF
authors.lastname: Kjeldsen
authors.forename: Yun Yong
authors.initials: YY
authors.lastname: Wang
authors.forename: Håvard
authors.initials: H
authors.lastname: Attramadal
authors.forename: Ansgar O
authors.initials: AO
authors.lastname: Aasen
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008026:Ligation; D008099:Liver / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D023421:Models, Animal; D009102:Multiple Organ Failure / Q000209:etiology / Q000276:immunology*; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*
chemical_list: C501849:CCN1 protein, rat; C526316:CCN2 protein, rat; D055515:Cysteine-Rich Protein 61; D055513:Connective Tissue Growth Factor