The combination of cigarette smoking and subnormal alpha 1 antitrypsin levels may explain the pulmonary spread in these two women who have what is usually a benign form of cutis laxa limited to the skin.
By studying molecular mechanisms of human disease-causing missense mutations within <i>a</i> subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation. cDNA-encoded FLAG-tagged human wildtype ATP6V0A2 (<i>a</i>2) and ATP6V0A4 (<i>a</i>4) subunits and their mutants, <i>a</i>2<sup>P405L</sup> (causing cutis laxa), and <i>a</i>4<sup>R449H</sup> and <i>a</i>4<sup>G820R</sup> (causing renal tubular acidosis, dRTA), were transiently expressed in HEK 293 cells.
These results suggest that increased gene expression levels of MMP-1, MMP-3 and MMP-9 in CL fibroblasts may contribute to the histopathological abnormality in CL.
Experiments of transient transfection of deleted or small substituted collagenase promoter-CAT constructs indicated that collagenase transcription in CL fibroblasts was activated the TPA-responsive element site of the collagenase promoter gene.
These results suggest that increased gene expression levels of MMP-1, MMP-3 and MMP-9 in CL fibroblasts may contribute to the histopathological abnormality in CL.
Although the levels of Jun and Fos gene expression did not differ from those observed in normal fibroblasts, AP-1-binding activity, as measured by the ability to bind to an oligonucleotide containing a TPA-responsive element, was significantly elevated in CL fibroblasts as compared with normal fibroblasts.
The 'Vitamin K deficit and elastolysis theory' posits that elastin degradation causes a rise in the vitamin K deficit and implies that vitamin K supplementation could be preventing elastin degradation.
To investigate the molecular mechanisms leading to cutis laxa in vivo, we generated transgenic mice by pronuclear injection of minigenes encoding normal human tropoelastin (WT) or tropoelastin with a cutis laxa mutation (CL).
This study investigates the expression profiles of genes responsible for the elastolysis in the dissected human aorta, especially those coding fibulin-1, matrix metalloproteinase-9 (MMP-9), and elastin.
Cutis laxa is an uncommon connective tissue disorder affecting the elastin fibers leading to lax and pendulous skin and in generalized form can present with systemic involvement.