The formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADs), including PAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We further demonstrated that PAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PAD2 resulted in attenuated elastogenesis in vitro and age-dependent emphysema in vivo. Mechanistically, citrullination protected FBLN5 from proteolysis and subsequent inactivation of its elastogenic activity. Furthermore, citrullinated but not native FBLN5 partially rescued in vitro elastogenesis in the absence of PAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.
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http://dx.doi.org/10.1016/j.matbio.2021.07.001 | DOI Listing |
Matrix Biol
November 2024
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Japan. Electronic address:
Fibrillin-1, an extracellular matrix (ECM) protein encoded by the FBN1 gene, serves as a microfibril scaffold crucial for elastic fiber formation and homeostasis in pliable tissue such as the skin. Aside from causing Marfan syndrome, some mutations in FBN1 result in scleroderma, marked by hardened and thicker skin which limits joint mobility. Here, we describe a tight skin phenotype in the Fbn1 mice carrying a corresponding variant of FBN1 in the hybrid1 domain that was identified in a patient with familial aortic dissection.
View Article and Find Full Text PDFDermatol Surg
December 2024
Cosmetic Laser Dermatology, San Diego, California.
Background: Injectable poly- l -lactic acid (PLLA-SCA) increases extracellular matrix to improve skin quality. The hip dell is an underappreciated element of gluteal aesthetics. Adipose tissue has roles in aesthetics and skin functioning.
View Article and Find Full Text PDFSci Rep
October 2024
Biomolecular Sciences Institute, Florida International University, Miami, FL, 33199, USA.
Elastic fibers are crucial for aortic valve (AoV) function and are generated and maintained by valvular interstitial cells (VICs). VICs exhibit diverse phenotypes, yet the specific subpopulation responsible for producing and regulating elastic fibers remains unclear. This gap in knowledge is significant, given that elastin (Eln) abnormalities lead to congenital AoV defects and initiate AoV diseases.
View Article and Find Full Text PDFNat Cardiovasc Res
August 2024
Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Valve remodeling is a process involving extracellular matrix organization and elongation of valve leaflets. Here, through single-cell RNA sequencing of human fetal valves, we identified an elastin-producing valve interstitial cell (VIC) subtype (apolipoprotein E (APOE), elastin-VICs) spatially located underneath valve endothelial cells (VECs) sensing unidirectional flow. APOE knockdown in fetal VICs resulted in profound elastogenesis defects.
View Article and Find Full Text PDFAdv Healthc Mater
October 2024
Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud university medical center, PO Box 9101, Nijmegen, 6500 HB, The Netherlands.
Elastin, a fibrous extracellular matrix (ECM) protein, is the main component of elastic fibers that are involved in tissues' elasticity and resilience, enabling them to undergo reversible extensibility and to endure repetitive mechanical stress. After wounding, it is challenging to regenerate elastic fibers and biomaterials developed thus far have struggled to induce its biosynthesis. This review provides a comprehensive summary of elastic fibers synthesis at the cellular level and its implications for biomaterial formulation, with a particular focus on dermal substitutes.
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