Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction
J. Clin. Invest. Jan Lammerding, et al. 113:370 doi:10.1172/JCI19670 [
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Figure 4Impaired mechanotransduction in lamin A/C–deficient cells. (
a)
Lmna–/– fibroblasts exhibited a significantly higher percentage of propidium iodide–positive cells than did WT cells (2.88% ± 0.49% vs. 1.14% ± 0.14%;
P < 0.01,
n = 7 [WT], 8 [
Lmna–/–]) after 24 hours of strain application (10% at 1 Hz). Differences in unstrained cells were not significant (
n = 9 [WT], 10 [
Lmna–/–]). (
b) Dual labeling with FITC-conjugated annexin V and propidium iodide uptake indicated that apoptotic (A) and necrotic (N) cell fractions are increased in
Lmna–/– cells following prolonged strain. Viable cells (V) are propidium iodide–negative and FITC-negative. Top left: WT unstrained control; top right:
Lmna–/– unstrained control; bottom left: WT cells after 10% strain for 24 hours; bottom right:
Lmna–/– cells after 10% strain for 24 hours. PI, propidium iodide. (
c)
Lmna–/– (KO) fibroblasts exhibited attenuated mechanical induction of
egr-1 and
iex-1 after 2 hours and 4 hours of strain (4%) compared with
Lmna+/+ cells (WT). Expression of GAPDH was not negatively affected. (
d) Cytokine–induced expression of
iex-1 was impaired in
Lmna–/– cells, while PMA responsiveness remained intact in
Lmna–/– cells.
