BEGIN:VCALENDAR
PRODID:-//Columba Systems Ltd//NONSGML CPNG/SpringViewer/ICal Output/3.3-
 M3//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20160205T131803Z
DTSTART:20160216T120000Z
DTEND:20160216T130000Z
SUMMARY:Cryptic laminin activity regulates matrix metalloproteinase expre
 ssion during epithelial-to-mesenchymal transition – towards a strategy t
 o target tissue fibrosis
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}u18y-ik9pw2
 h7-tlellz
DESCRIPTION:Abstract:\nThe remodelling of the basement membrane (BM) – an
  integral part of the epithelial-to-mesenchymal transition (EMT) - invol
 ves constant modulation of integrin-BM protein interactions facilitated 
 by the structural and conformational diversity of different BM proteins.
  During remodelling\, cryptic sites can become biologically active by pr
 oteolytic processing through matrix metalloproteinases (MMPs) or by cell
 -induced mechanical strain. These cryptic sites mediate a variety of dif
 ferent biological activities which are still widely unexplored\, especia
 lly in pathological phenotypes.  The exploration of molecular mechanisms
  involved in the interplay of the BM and epithelial cells is critical to
  understand tissue remodelling as well as to grasp the complexity of EMT
 -related pathologies such as tissue fibrosis.\n\nWe have recently shown 
 that a fragment of the b1-chain of laminin modulates the expression of M
 MP2 in human and mouse embryonic stem cells following the initiation of 
 EMT (1). This 60kDa fragment is released by MMP2 processing and it exhib
 its specific binding sites for a3b1-integrin thereby triggering changes 
 in EMT-related gene expression. This specific interaction causes a signi
 ficant down-regulation of the expression and activity of MMP2. Given the
  similarities between EMT molecular pathways during development and tiss
 ue fibrosis\, we hypothesized that similar inhibitory mechanisms could b
 e switched on in epithelial cells undergoing TGFb-induced EMT. Here\, we
  show that the fragment indeed modulates EMT gene expression in this set
 ting. The interaction of the b1-fragment with mesothelial tissue of a mo
 use peritoneal membrane undergoing TGFb1-induced fibrosis\, rescues tiss
 ue integrity by decreasing the amount of active MMP2 released by the tis
 sue. Of importance\, the fragment does not act on extracellular MMP2\, b
 ut rather interferes with key EMT pathways. These results demonstrate th
 e important role of cryptic basement membrane activities in the patholog
 ical differentiation of cells and suggests a feedback mechanism regulati
 ng MMP activities during matrix remodelling.\n\n(1) Horejs C.-M.\, Serio
  A.\, Purvis A.\, Gormley A.\, Bertazzo S.\, Poliniewicz A.\, Wang A.\, 
 DiMaggio P.\, Hohenester E.\, Stevens M.M.\,  PNAS (2014)\, 111 (16) 590
 8-5913
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Lecture Theatre\, Michael Smith Building\, Manchester
END:VEVENT
END:VCALENDAR