In contrast to lung fibroblasts--no signs of senescence in skin fibroblasts of patients with emphysema.
Smoking is known to be linked to skin ageing and there is evidence for premature senescence of parenchymal lung fibroblasts in emphysema. To reveal whether the emphysema-related changes in cellular phenotype extend beyond the lung, we compared the proliferation characteristics of lung and skin fibroblasts between patients with and without emphysema. Parenchymal lung fibroblasts and skin fibroblasts from the upper torso (thus limiting sun exposure bias) were obtained from patients without, or with mild, or with moderate to severe emphysema undergoing lung surgery. We analysed proliferation rate, population doublings (PD), staining for senescence-associated beta-galactosidase (beta-gal) and gene expression of IGFBP-3 and IGFBP-rP1. Population doubling time of lung fibroblasts differed between control, mild, and moderate to severe emphysema (median (IQR) 29.7(10.0), 33.4(6.1), 44.4(21.2) h; p=0.012) and staining for beta-gal was elevated in moderate to severe emphysema. Compared to control subjects, skin fibroblasts from patients with emphysema did not differ with respect to proliferation rate, PD and beta-gal staining, and showed a lower abundance of mRNA for IGFBP-3 and -rP1 (p<0.05, each). These results suggest that the induction of a senescent fibroblast phenotype by cigarette smoke, as observed in emphysema, primarily occurs in the lung.
Müller
Kai-Christian
KC
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Paasch
Kirsten
K
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Feindt
Beke
B
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Welker
Lutz
L
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Watz
Henrik
H
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Weise
Michael
M
Department of Pneumology, Lindenhofspital, 3001 Bern, Switzerland.
Schmid
Ralph A
RA
Department of Thoracic Surgery, Inselspital, 3001 Bern, Switzerland.
Nakashima
Masaki
M
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Branscheid
Detlev
D
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Magnussen
Helgo
H
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
Jörres
Rudolf A
RA
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, 80336 Munich, Germany.
Holz
Olaf
O
Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Woehrendamm 80, 22927 Grosshansdorf, Germany.
D000368:Aged; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D012907:Smoking / Q000378:metabolism / Q000473:pathology; D001616:beta-Galactosidase / Q000378:metabolism
D018969:Insulin-Like Growth Factor Binding Proteins; D001616:beta-Galactosidase