LINCing Senescence and Nuclear Envelope Changes
Abstract
:1. Introduction
1.1. Senescence
1.2. The LINC Complex
2. LINC Proteins in Senescence
2.1. Nesprin-1
2.2. Nesprin-2
2.3. Nesprin-3
2.4. SUN1/SUN2
3. The LINC Complex, Mechanical Stress and Senescence
4. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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LINC Protein | Model/Cell Line | Mode of Senescence Induction | Cellular Mechanisms/Structures Affected | Ref’s |
---|---|---|---|---|
Nesprin-1 | Embryonic mouse mesenchymal stem cell line (CH310T1/2) |
| Increase (↑) DNA damage (DSBs) due to DNA mismatch repair (MMR) impairment
| [48,49] |
Human dermal fibroblasts (HFs) |
|
Knockdown
:
Decrease (↓) MMR (etoposide)
| ||
Human colorectal carcinoma cell line (DLD-1). These cells are Nesprin-1 deficient. | N/A |
Compared to normal human fibroblast
:
| ||
Human hepatocellular carcinoma cell lines (Hep3B, Huh7) These cells have low endogenous Nesprin-1 expression. |
| Non-Treated (comparing Hep3B and Huh7 to normal liver cells)
| ||
Nesprin-2 variant (β∆KASH1) | Human aortic vascular smooth muscle cells (VSMCs) | Population doublings (PDs) | Presenescence:
| [50] |
|
| |||
|
| |||
| Proliferative:
| |||
| Presenescent:
Proliferative: G2/M checkpoint failure:
| |||
Nesprin-2 | Aged-Pluripotent stem cells (a-iPSCs) | iPSCs cultured for more than one year | mRNA expression levels:
| [51] |
HGPS dermal fibroblasts HGPS mice interfollicular epidermis (IFE) | N/A |
Postnatal day 4 (mice):
Human HGPS fibroblasts:
| [52] | |
SUN1/2 | SUN1/2-/- MEFs | N/A | ↓ Perinuclear heterochromatin compared to wild-type MEFs | [53] |
| Compared to wild type MEFs:
| |||
|
| |||
Mmp14-/- mouse embryonic fibroblasts (MEFs) | N/A |
Perinuclear and nuclear region:
| [54] | |
LMNA-/- mouse embryonic fibroblasts (MEFs) | N/A |
| [55] | |
Lmna∆9 mutant MEFs | N/A | Irregularly shaped nucleus with frequent herniations and blebs that were reduced in LMNA/SUN1 DKO MEFs | ||
Hutchinson-Gilford progeria syndrome (HGPS) human skin fibroblasts | N/A | Compared to normal human fibroblast:
| ||
Hutchinson-Gilford progeria syndrome (HGPS) human skin fibroblasts | N/A |
Structural changes:
| [56] | |
HeLa cells | Progerin overexpression |
| ||
Progerin overexpression & SUN1 KD |
|
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Meqbel, B.R.M.; Gomes, M.; Omer, A.; Gallouzi, I.E.; Horn, H.F. LINCing Senescence and Nuclear Envelope Changes. Cells 2022, 11, 1787. https://doi.org/10.3390/cells11111787
Meqbel BRM, Gomes M, Omer A, Gallouzi IE, Horn HF. LINCing Senescence and Nuclear Envelope Changes. Cells. 2022; 11(11):1787. https://doi.org/10.3390/cells11111787
Chicago/Turabian StyleMeqbel, Bakhita R. M., Matilde Gomes, Amr Omer, Imed E. Gallouzi, and Henning F. Horn. 2022. "LINCing Senescence and Nuclear Envelope Changes" Cells 11, no. 11: 1787. https://doi.org/10.3390/cells11111787