Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2

• Main Authors: Alice-Anaïs Varlet, Emmanuèle Helfer, Catherine Badens
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Cells
• Subjects: lamin A/C; FPLD2; laminopathies; signaling pathway; adipocytic cells; endothelial cells
• Online Access: https://www.mdpi.com/2073-4409/9/9/1947

Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the <i>LMNA</i> gene, with at least 20 mutations that are considered pathogenic. <i>LMNA</i> encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis.