Fibroblast apoptosis in a patient affected by lamellar ichthyosis.
BACKGROUND
Lamellar ichthyosis (LI) is a congenital recessive skin disorder characterized by generalized scaling and hyperkeratosis. The pathology may be caused by mutations in transglutaminase 1 (TGM1) gene that encodes an enzyme critical for terminally differentiating keratinocytes. Because of evidences that transglutaminase enzymes are involved in programmed cell death, we investigated morphological and biochemical apoptotic parameters in cultured skin fibroblasts from a patient with a severe LI and homozygous for the TGM1 R142H mutation.


METHODS
The principle apoptotic signals (mitochondrial membrane potential, analysis of oxygen consumption, DNA fragmentation and Bax/Bcl-2 gene expression) were analyzed in cultured fibroblasts from a LI patient, his mother (TGM1 mutation carrier) and a control subject.


RESULTS
LI fibroblasts showing a reduction of fibronectin expression evidenced a strong inhibition of oxygen consumption, a dramatic drop in the mitochondrial membrane potential (Delta psi(m)), and a higher apoptotic index.


CONCLUSIONS
The present results suggest a possible connection between the alterations in the keratinization process leading to LI and the observed increased fibroblast apoptosis.
Tavian
Daniela
D
Laboratory of Human Molecular Biology and Genetics, Catholic University of the Sacred Heart, Milan, Italy.
Colombo
Roberto
R
Misiti
Francesco
F
Ena
Pasquale
P
Ena
Luca
L
Sampaolese
Beatrice
B
Giardina
Bruno
B
Clementi
Maria E
ME
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D019069:Cell Respiration / Q000502:physiology; D019938:Cyclin D1 / Q000096:biosynthesis; D053938:DNA Fragmentation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008969:Molecular Sequence Data; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D011503:Transglutaminases; C105804:transglutaminase 1