The Role of STAT 3 in Tissue Fibrosis

Li      Ma; Shougang      Zhuang

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor and has been implicated in cell proliferation, survival and differentiation. Recent studies demonstrate that STAT3 activity is persistently elevated in patients with some chronic disorders, and required for the development and progression of fibrosis in a variety of tissues including kidney, bone marrow and skin. On the other hand, STAT3 is implicated in tissue protection against fibrosis in the heart following acute injury. Moreover, STAT3 can either promote or protect against tissue fibrosis in chronic liver disease models, depending on etiologies. The underlying mechanisms by which STAT3 mediates those cellular events are not fully understood, but the profibrotic action of STAT3 is mostly associated with activation and proliferation of fibroblasts, deposition of excessive extracellular matrix proteins, and overproduction of some cytokines. In this review article, we discuss the role of STAT3 in tissue fibrosis and the effect of the STAT3 pathway inhibition on the proliferation and activation of fibroblasts in vitro and fibrogenesis in various animal models.

Keywords: STAT3, fibroblasts, tissue fibrosis, proliferation, cytokines, kidney, bone marrow, organ failure, fibroproliferative diseases, pathogenesis of tissue, hardening, extracellular matrix, autoimmune, allergic responses, cytokines/growth factors, growth factor, (TGF), hematopoetic factors, fibrogenic actions, cytoplasmic transcription, coiled-coil, DNA binding, C-terminal transactivation, protein-protein interactions, Receptors, tyrosine kinase, phosphorylation, Renal Interstitial Fibrosis, glomerular sclerosis, glomerulonephritis, IgA, epithelial cells, unilateral ureteral obstruction (UUO), obstructive nephropathy, smooth actin, inflammatory cells, diabetic, hyperfiltration, urinary albumin excretion, hemodynamic, visceral epithelium, interstitial edema, nephron, chronic autoimmune diseases or rachitis, myeloid metaplasia, syndrome, neutrophils, Spinal Cord Injury, Astrocytes, glial cells, central nervous system, traumatic injuries, Immunofluorescence, motor recovery, Keloid, skin lesions, collagen deposition, migration, cirrhosis, metabolic disorders, parasitic diseases, hepatic stellate cells, platelet derived growth factor (PDGF), oxidative stress, hyperactivation, Idiopathic pulmonary fibrosis (IPF), hypertension, myocardial infarction, aging, bleomycin injury, carbon tetrachlorideinduced, leukocytes