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ADAM17 is a member of the disintegrin and metalloproteinase (ADAM) family of transmembrane proteases with immunoregulatory activity in multiple signaling pathways. The functional ADAM17 is involved in the shedding of the ectodomain characterizing many substrates belonging to growth factors, cytokines, receptors, and adhesion molecules. The ADAM17-dependent pathways are known to be crucial in tumor development and progression and in the modulation of many pathological and physiological processes. In the last decade, ADAM17 was considered the driver of several autoimmune pathologies, and numerous substrate-mediated signal transduction pathways were identified. However, the discoveries made to date have led researchers to try to clarify the multiple mechanisms in which ADAM17 is involved and to identify any molecular gaps between the different transductional cascades. In this review, we summarize the most recent updates on the multiple regulatory activities of ADAM17, focusing on reported data in the field of autoimmunity.
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http://dx.doi.org/10.3390/cells13242092 | DOI Listing |
Int J Mol Sci
July 2025
Department of Biochemistry, Showa Medical University Graduate School of Medicine, Tokyo 142-8555, Japan.
Recent advances have highlighted the multifaceted roles of the lymphatic vasculature in immune cell trafficking, immunomodulation, nutrient transport, and fluid homeostasis. Beyond these physiological functions, lymphatic vessels are critically involved in pathologies such as cancer metastasis and lymphedema, rendering their structural and functional regulation of major interest. Emerging evidence suggests that limited proteolysis is a key regulatory mechanism for lymphatic vascular function.
View Article and Find Full Text PDFJ Clin Med
July 2025
Division of Medical Biology, Faculty of Nursing and Midwifery, Wroclaw Medical University, 50-368 Wrocław, Poland.
SARS-CoV-2 infection has been associated with long-term health consequences, including dysregulation of the renin-angiotensin-aldosterone system (RAAS). This study aimed to evaluate long-term changes in selected RAAS-related biochemical parameters in repeat convalescent plasma donors, focusing on enzymes and peptides involved in vascular regulation and inflammation. Thirty repeat convalescent plasma donors were enrolled, each providing four serum samples at defined time points post-infection.
View Article and Find Full Text PDFJ Extracell Vesicles
July 2025
INSERM UMR-S 1124, Paris, France.
Small extracellular vesicles (SEVs) are involved in diverse functions in normal and pathological situations, including intercellular communication, immunity, metastasis and neurodegeneration. Cell release of SEVs is assumed to occur passively right after multivesicular bodies of the endocytic pathway fuse with the plasma membrane. We show here that the completion of SEV release depends on membrane-bound ADAM10 and ADAM17 sheddases that promote the detachment of SEVs from the cell surface by catalysing the cleavage of adhesion proteins of the SEV membrane.
View Article and Find Full Text PDFChronic ocular surface disease (OSD) is characterized by corneal epitheliopathy, reduced barrier function and loss of nerves, accompanied by persistent inflammation. Current treatments offer limited relief and there is no approved therapy that promotes neurosensory regeneration in OSD. Here, we tested the therapeutic efficacy of clusterin (CLU), a molecular chaperone and MMP9 inhibitor found in tears, in -deficient mice, a preclinical model of autoimmune dry eye associated with Sjögren's disease (SjD).
View Article and Find Full Text PDFMol Divers
June 2025
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, PR China.
The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to its high metastatic properties. Hence, metastasis inhibition might provide a reliable strategy for HCC treatment. As its pivotal role in the tumor cell proliferation, survival and metastasis, a disintegrin and metalloproteinase 17 (ADAM17) has become an attractive target for cancer therapy.
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