{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T14:47:03Z","timestamp":1770475623067,"version":"3.49.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6301,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Latent transforming growth factor \u03b2 binding protein (LTBP), a component of the extracellular matrix (ECM) of various tissues, is important for the secretion of TGF-\u03b2 and, furthermore, for the storage of TGF-\u03b2 in ECM. The proteolytic cleavage of LTBP is assumed to be the prerequisite for the activation of TGF-\u03b2. We investigated the mRNA expression pattern of the three LTBP isoforms (LTBP-1, -2, -3) and the protein distribution of the components of the large latent TGF-\u03b2 complex, namely LTBP-1 and -2, latency-associated protein (LAP), and TGF-\u03b2, in human liver using reverse-transcription polymerase chain reaction (RT-PCR) and immunhistochemical alkaline phosphatase anti-alkaline phosphatase (APAAP) staining. Parts of explanted livers diagnosed as hepatitis B, hepatitis C, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) and normal liver tissue were examined. LTBP transcripts were detected in the same manner in all liver specimens. Interestingly, we found a new splice variant of LTBP-1 (LTBP-1D), in which the sequence coding for the proteinase-sensitive hinge region is deleted. The corresponding parts of the human LTBP-2 and LTBP-3 cDNA coding for the hinge region were sequenced and show neither similar proteinase cleavage sites nor deleted cDNA sequences. The proposed proteinase cleavage site of mouse LTBP-3 seems not to be conserved in the human LTBP-3 gene. By immunohistochemistry, LTBP-1, -2, and LAP were detectable in normal and diseased livers and showed a different staining pattern for both LTBP isoforms. By contrast, TGF-\u03b2 showed a spotted staining pattern in diseased livers only, predominantly in the area of parenchymal cells that are close to fibrotic tissue. This strongly suggests the release of active TGF-\u03b2 from preexisting latent complexes. The LTBP-1D splice variant, which is probably less sensitive against proteolytic degradation and therefore may protect TGF-\u03b2 from activation, may have importance for modulating the biological activity of TGF-\u03b2 in normal and diseased liver.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510270619","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:53:37Z","timestamp":1090972417000},"page":"1592-1599","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":31,"title":["Analysis of the expression pattern of the latent transforming growth factor \u03b2 binding protein isoforms in normal and diseased human liver reveals a new splice variant missing the proteinase-sensitive hinge 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