Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic potential of an integral membrane protein, caveolin-1. While caveolin-1 has been widely studied for its role in the regulation of cell signaling and endocytosis, its possible implication in fibrosis remains largely unclear. In this review we survey involvement of caveolin-1 in various cellular processes and highlight different aspects of its antifibrotic activity. We hypothesize that caveolin-1 conveys a homeostatic function in the process of fibrosis by (a) regulating TGF-β1 and its downstream signaling; (b) regulating critical cellular processes involved in tissue repair, such as migration, adhesion and cellular response to mechanical stress; and (c) antagonizing profibrotic processes, such as proliferation. Finally, we consider this homeostatic function of caveolin-1 as a possible novel approach in treatment of fibroproliferative diseases.
Homeostasis of hematopoietic stem and progenitor cells (HSPC) is controlled by a combination of biochemical and biophysical environmental cues in the bone marrow (BM) niche, where a tight balance of quiescence and proliferation of HSPC is maintained. Specifically, alongside soluble factors and extracellular matrix (ECM) proteins, spatial confinement and ECM stiffness have been recognized to be critical for regulation of HSPC fate. Here we employ a modular, glycosaminoglycan (GAG)-based biohybrid hydrogel system to balance proliferation of human HSPC and maintenance of quiescent hematopoietic stem cells (HSC) through simultaneous regulation of exogenous biochemical and biophysical cues. Our results demonstrate that HSPC respond to increased spatial confinement with lowered proliferation and cell cycling, which results in higher frequency of quiescent LTC-IC (long-term culture initiating cells), while GAG-rich 3D environments further support maintenance of the cells.
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