LitCoin-sentences  

PubMed:28468941 JSONTXT 24 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-215 Sentence denotes Aberrant caveolin-1-mediated Smad signaling and proliferation identified by analysis of adenine 474 deletion mutation (c.474delA) in patient fibroblasts: a new perspective on the mechanism of pulmonary hypertension.
T2 216-346 Sentence denotes A heterozygous caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH).
T3 347-513 Sentence denotes This frameshift mutation leads to a caveolin-1 protein that contains all known functional domains but has a change in only the final 20 amino acids of the C-terminus.
T4 514-610 Sentence denotes Here we studied how this mutation alters caveolin-1 function, using patient-derived fibroblasts.
T5 611-722 Sentence denotes Transmission electron microscopy showed that fibroblasts carrying the c.474delA mutation form typical caveolae.
T6 723-901 Sentence denotes Expression of mutated caveolin-1 in caveolin-1-null mouse fibroblasts failed to induce formation of caveolae due to retention of the mutated protein in the endoplasmic reticulum.
T7 902-1010 Sentence denotes However, coexpression of wild-type caveolin-1 with mutated caveolin-1 restored the ability to form caveolae.
T8 1011-1154 Sentence denotes Importantly, fibroblasts carrying the mutation showed twofold increase in proliferation rate associated with hyperphosphorylation of Smad1/5/8.
T9 1155-1223 Sentence denotes This mutation impaired the antiproliferative function of caveolin-1.
T10 1224-1377 Sentence denotes Inhibition of type I TGFβ receptors ALK1/2/3/6 responsible for phosphorylation of Smad1/5/8 reduced the hyperproliferation seen in c.474delA fibroblasts.
T11 1378-1706 Sentence denotes These results demonstrate the critical role of the final 20 amino acids of caveolin-1 in modulating fibroblast proliferation by dampening Smad signaling and suggest that augmented Smad signaling and fibroblast hyperproliferation are contributing factors in the pathogenesis of PAH in patients with caveolin-1 c.474delA mutation.