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Background: The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamin. A- and B-type lamins are the major components of the nuclear lamina. Lamins function in many nuclear activities. The role of lamin A and transcription factors (NF-kB) as anti-apoptotic is well documented. Recently, lamin A has also been considered as a mechanosensor protein that is able to maintain nuclear integrity from mechanical insults. We aimed to verify how lamin A expression varies in healthy cuff cells and in those with different-sized tears where various mechanical stresses are present.
Methods: Forty-three patients with rotator cuff tear (RCT) [23M-20F, mean age (SD): 63.5 (6.1)] were enrolled. Tissue samples excised from the most medial point of tear margins were analyzed for lamin A expression by immunohistochemistry. Controls were represented by samples obtained by normal supraspinatus tendons excised from patients submitted to reverse shoulder prosthesis implant [8M-7F, mean age (SD): 67.9 (7.1)]. The intensity of staining was graded, and an H-score was assigned. Statistical analysis was performed.
Results: Our study revealed a moderate intensity of lamin A in the healthy cuff tendons, a higher expression of this protein in the small tears, and a significant decrease of lamin A with increasing tear size (p < 0.0001).
Conclusions: Our study emphasizes the importance of early repair of small RCTs since nuclear stability is maintained, and the cellular function is protected by lamin A overexpression. High re-tear of massive cuff repair could be due to cellular apoptosis and nuclear modifications induced by lamin A lack.
Level Of Evidence: III.
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http://dx.doi.org/10.1186/s13018-021-02569-1 | DOI Listing |
Nucleic Acids Res
September 2025
Department of Biosciences & Bioengineering, IIT Bombay, Mumbai 400076, India.
Embryonic stem cells (ESCs), which are susceptible to DNA damage, depend on a robust and highly efficient DNA damage response (DDR) mechanism for their survival. However, the implications of physical force-mediated DNA damage on ESC fate remain unclear. We show that stiffness-dependent spreading of mouse ESCs (mESCs) induces DNA damage through nuclear compression, with DNA damage causing differentiation through Lamin A/C.
View Article and Find Full Text PDFSci China Life Sci
September 2025
The Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, 100871, China.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare progeroid disorder, and approximately 90% of cases are caused by LMNA mutation that yields the lamin A/C variant progerin. Progerin is toxic, and its clearance and disruption have positive benefits on HGPS cells and mice and even HGPS patients. However, accelerating progerin clearance is still an unaddressed issue.
View Article and Find Full Text PDFBMB Rep
September 2025
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499; Department of Biomedical Sciences, The Graduate School of Ajou University, Suwon 16499; BK21 R&E Initiative for Advanced Precision Medicine, Ajou University School of Medicine, Suwon 16499, Korea.
Altered nuclear morphology, one of the characteristics of cancer cells, is often indicative of tumor prognosis. While reactive oxygen species (ROS) are known to induce nuclear morphology changes, mechanisms underlying these effects remain elusive, particularly regarding nuclear assembly. We hypothesized that mitotic cells might exhibit increased susceptibility to ROSinduced nuclear deformation due to the dynamic nature of nuclear envelope during mitosis, i.
View Article and Find Full Text PDFCell Mol Life Sci
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Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Chromatin, the spatial organizer of genomic DNA, is hierarchically folded into higher-order structures to facilitate DNA compaction, enabling genome surveillance. Understanding the organization and function of the three-dimensional (3D) genome is critical to profile chromatin accessibility and functional interactions that govern gene regulation across multiple biological processes, including aging and one of its hallmarks, cellular senescence. Cellular senescence constitutes a defensive stress response to various intrinsic and extrinsic stimuli, preserving cellular and organismal homeostasis through a generally irreversible cell cycle arrest.
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August 2025
Program in Chemical Biology, Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA; Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. El
Nuclear lamins are type V intermediate filament proteins to support the mechanical stability of mammalian cell nucleus. They also participate in various signaling activities in the cells. We recently discovered substituted pyrroloquinazoline LBL1 as the first small molecule to directly target nuclear lamins despite their poor druggability.
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