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Interleukin 11 (IL11) is an elusive member of the IL6 family of cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 is redundant for haematopoiesis and toxic. In this review, the reasons that led to the original misunderstandings of IL11 biology, which are now understandable, are explained with particular attention on the use of recombinant human IL11 in mice and humans. Following tissue injury, as part of an evolutionary ancient homeostatic response, IL11 is secreted from damaged mammalian cells to signal via JAK/STAT3, ERK/P90RSK, LKB1/mTOR and GSK3β/SNAI1 in autocrine and paracrine. This activates a program of mesenchymal transition of epithelial, stromal, and endothelial cells to cause inflammation, fibrosis, and stalled endogenous tissue repair, leading to organ failure. The role of IL11 signalling in cell- and organ-specific pathobiology is described, the large unknowns about IL11 biology are discussed and the promise of targeting IL11 signalling as a therapeutic approach is reviewed.
Interleukin 11 (IL11) is an elusive member of the IL6 family of cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 is redundant for haematopoiesis and toxic. In this review, the reasons that led to the original misunderstandings of IL11 biology, which are now understandable, are explained with particular attention on the use of recombinant human IL11 in mice and humans. Following tissue injury, as part of an evolutionary ancient homeostatic response, IL11 is secreted from damaged mammalian cells to signal via JAK/STAT3, ERK/P90RSK, LKB1/mTOR and GSK3β/SNAI1 in autocrine and paracrine. This activates a program of mesenchymal transition of epithelial, stromal, and endothelial cells to cause inflammation, fibrosis, and stalled endogenous tissue repair, leading to organ failure. The role of IL11 signalling in cell- and organ-specific pathobiology is described, the large unknowns about IL11 biology are discussed and the promise of targeting IL11 signalling as a therapeutic approach is reviewed.
Diabetic kidney disease (DKD) is a global health burden and the leading cause of end-stage renal disease. Its clinical management focuses on controlling hyperglycemia, hypertension, and hyperlipidemia. While the progression of DKD can be slowed with intervention, it cannot be stopped or reversed yet. The pathogenesis of DKD is complex, with an interplay of numerous signaling pathways, and research continues to decipher the players and their role, be it beneficial or pathogenic. Inflammation is an essential defense of our bodies against internal or external insults. The injuries that trigger inflammation range from pathogenic infections and wounds to dysregulated metabolism. Inflammation is helpful only if it is controlled and subsides after it has helped defend the individual against the insult. Uncontrolled or chronic inflammation is recognized as a contributor to numerous chronic diseases. Dysregulated inflammation plays a role in multiple aspects of DKD: glomerular hyperfiltration, mesangial expansion, podocyte injury, tubular injury, basement membrane thickening, fibrosis, and scarring. Since inflammation plays an integral role in the progression of DKD, targeting it for therapy is also reasonable. There is a growing trend of targeting inflammation as a therapeutic approach, with new targets being discovered and evaluated drugs every year. The exponential increase in literature necessitates a comprehensive summary of current information, hence this review.
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