Partial Epithelial-to-Mesenchymal Transition and Other New Mechanisms of Kidney Fibrosis

Myofibroblast accumulation in kidney fibrosis is due to the proliferation of the resident interstitial fibroblasts and the differentiation from bone marrow progenitors, tubular epithelial cells, and peritubular endothelial cells. Non-reversible epigenetic modifications, such as methylation, sustain and perpetuate the activated state of interstitial myofibroblasts. EMT contributes to the loss of functional parenchyma by impairing the ability of tubular epithelial cells to proliferate and by compromising their functional properties. Injured tubular epithelial cells display dramatic metabolic rearrangements, such as a profound suppression of fatty acid oxidation, which highly impacts on the regeneration capacity and fibrogenesis. Macrophages, lymphocytes, dendritic cells and mast cells are key players in mediating inflammation and immune response in kidney fibrosis. The balance between their pro-fibrogenic and anti-inflammatory functions likely determines the final fibrotic outcome. Kidney fibrosis is the unavoidable consequence of chronic kidney disease irrespective of the primary underlying insult. It is a complex phenomenon governed by the interplay between different cellular components and intricate networks of signaling pathways, which together lead to loss of renal functionality and replacement of kidney parenchyma with scar tissue. An immense effort has recently been made to understand the molecular and cellular mechanisms leading to kidney fibrosis. The cellular protagonists of this process include myofibroblasts, tubular epithelial cells, endothelial cells, and immune cells. We discuss here the most recent findings, including partial epithelial-to-mesenchymal transition (EMT), in the initiation and progression of tissue fibrosis and chronic kidney disease (CKD). A deep understanding of these mechanisms will allow the development of effective therapies. Kidney fibrosis is the unavoidable consequence of chronic kidney disease irrespective of the primary underlying insult. It is a complex phenomenon governed by the interplay between different cellular components and intricate networks of signaling pathways, which together lead to loss of renal functionality and replacement of kidney parenchyma with scar tissue. An immense effort has recently been made to understand the molecular and cellular mechanisms leading to kidney fibrosis. The cellular protagonists of this process include myofibroblasts, tubular epithelial cells, endothelial cells, and immune cells. We discuss here the most recent findings, including partial epithelial-to-mesenchymal transition (EMT), in the initiation and progression of tissue fibrosis and chronic kidney disease (CKD). A deep understanding of these mechanisms will allow the development of effective therapies. a temporary failure of kidney functionality, typically caused by decreased blood flow, toxic exposure, or obstruction. As the original insult is removed, repair and resolution occur. Failure of a complete repair in AKI highly predisposes a patient to progress into chronic kidney disease. a condition characterized by the progressive loss of the kidney functionality. It is clinically defined by reduced glomerular filtration rate and increased albumin excretion. The major hallmark of CKD is extensive fibrosis, which leads to the loss of functional tubules and the gradual replacement of functional parenchyma with scar tissue. The two most common causes of CKD are diabetes and high blood pressure. CKD can progress to end-stage renal disease. the final stage of CKD characterized by the permanent and almost complete failure of the kidneys. Kidney functionality is below 10–15% of the normal capacity and is not enough to meet the daily body needs. The only available treatments for ESRD are dialysis and kidney transplantation. a surgical procedure consisting of clamping the left renal pedicle for 30 minutes followed by the removal of the clamp. It induces ischemia of the left kidney by a temporary interruption of the blood supply. As a consequence of the injury, massive fibrosis is generated, which usually resolves over the course of 7–10 days. surgical procedure consisting of ligation of one ureter, leading to the upstream accumulation of urine with a consequent increase in intrarenal pressure, exposure of tubular epithelial cells to toxins, and inflammation. It causes an obstructive nephropathy characterized by extensive tubular atrophy, interstitial fibrosis, and immune infiltration. highly specialized epithelial cells lining the inner side of the renal tubules that constitute the nephron, the functional unit of the kidney.