Fibroblasts in fibrosis: novel roles and mediators
TLDR
Many common fibroblast-related features across various physiological and pathological protracted processes are recognized and a new appreciation has emerged for the role of non-cancerous fibro Blast interactions with tumors in cancer progression.Abstract:
Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM) characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types—most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of noncancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve nonspecific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.read more
Citations
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Journal ArticleDOI
Idiopathic pulmonary fibrosis
Fernando J. Martinez,Harold R. Collard,Annie Pardo,Ganesh Raghu,Luca Richeldi,Moisés Selman,Jeffrey J. Swigris,Hiroyuki Taniguchi,Athol U. Wells +8 more
TL;DR: The biological processes underlying IPF are thought to reflect an aberrant reparative response to repetitive alveolar epithelial injury in a genetically susceptible ageing individual, although many questions remain on how to define susceptibility.
IL-13受体α2降低血吸虫病肉芽肿的炎症反应并延长宿主存活时间[英]/Mentink-Kane MM,Cheever AW,Thompson RW,et al//Proc Natl Acad Sci U S A
TL;DR: 曼氏血吸虫感染后,宿主活化CD4^+Th2细胞L分泌IL-4、IL-5和 IL-13。
Journal ArticleDOI
Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications
TL;DR: Specific mechanistic principles of fibrosis regression involve the resolution of chronic tissue injury, the shift of inflammatory processes towards recovery, deactivation of myofibroblasts and finally fibrolysis of excess matrix scaffold.
Journal ArticleDOI
Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance.
Micol E. Fiori,Simone Di Franco,Lidia Villanova,Paola Bianca,Giorgio Stassi,Ruggero De Maria +5 more
TL;DR: The most recent identified mechanisms underlying CAF-mediated control of tumor progression and therapy resistance, which include induction of the epithelial-to-mesenchymal transition (EMT), activation of survival pathways or stemness-related programs and metabolic reprogramming in tumor cells are dissected.
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