TGF‐β promotes the formation of pyridinoline cross‐links in fibrosis via the induction of LH2 expression

Abstract

including 15 graduate students) and 53 nonmembers (including 16 graduate students). There were 17 invited speakers, with three from the USA, five from the EU and five from the UK.Jean Schwarzbauer (Princeton University, USA) opened the meeting by describing her recent findings concerning the events that control fibronectin (Fn) matrix assembly. The assembly of Fn matrix fibrils is influenced by extracellular factors such as availability of Fn and other matrix molecules, and intracellular signalling pathways mediated by integrin receptors. Jean's group has investigated two kinases downstream of integrin receptors, focal adhesion kinase (FAK) and pp60-Src. Mouse fibroblasts lacking FAK were found to assemble reduced amounts of Fn fibrils. Src family kinases phosphorylate FAK, and it was found that fibroblasts without Src family kinases (SYF cells) or wild-type cells treated with an Src inhibitor (PP1) also lack Fn matrix. The extracellular influence of tenascin-C was also discussed. In fibroblasts on a 3D Fn matrix, FAK was constitutively phosphorylated, whereas in the presence of tenascin-C, FAK is transiently activated, and there is a reduction in the assembly of Fn matrix fibrils. Other aspects of integrin-Fn interactions were also described, including the stimulation of Fn matrix formation by dexamethasone in the tumourgenic cell line HT1080.Karl Kadler (University of Manchester) summarized findings on the molecular and cellular basis of collagen fibrillogenesis. The talk focussed on the sorting and secretion of type-I collagen in organ cultures of embryonic chick tendon. It Int.