The extracellular matrix is integral to tissue biology, and alteration of its functions has been implicated in a host of chronic conditions including obesity [8], [18].
The suggestion that the matrigenic actions of growth factors for intact mesenchymal tissue are an integral part of mitogenic signaling is supported by the observation that surfaces derivatized with ProNectin, an artificial mimic of the RGD attachment domain of fibronectin, stimulated the proliferation of embryonic mesenchyme in the absence of exogenous growth factors.
41 This mechanism is increasingly recognized as an integral part of tissue fibrogenesis after injury, but seems to play a limited role during normal tissue repair.
Stromal vascular cells include non-adipose cell types such as preadipocytes, macrophages and lymphocytes that are integral to adipose tissue biology and whose functions are altered in obesity [8], [15], [16], [17], [51], [52], [53].
Moreover, little is known about the functions of homeobox genes in relation to obesity, though it has been suggested that they affect processes that are integral to adipose tissue function, such as adipogenesis [30], [31].
The development of biocompatible scaffolds acting as an extracellular matrix to serve as a substrate for sustaining cell growth, survival, differentiation, and other biologically relevant functions has become an integral aspect of tissue engineering.
EBV plays an integral role in tissue inflammation and NPC development.
This process is increasingly being recognized as an integral part of tissue fibrogenesis after injury, and could be an adaptive response of epithelial cells to an unfavorable microenvironment [ 20].
Elevated levels of signals that protect against uncontrolled cellular proliferation and promote cellular differentiation (e.g., follistatin) were also detected and are integral functions in tissue rebuilding and repair (Sengupta et al, 2014).
Stem and progenitor cells would be obvious candidates as these cells not only lose telomeres with advancing age, but also appear to be integral to preserving tissue damaged by age.
Finally, epithelial- and endothelial-to-mesenchymal transition (EMT), a process by which differentiated or malignant epithelial and endothelial cells undergo a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury, particularly in the kidney [ 34].
