The role of macrophages in the progression from acute kidney injury to chronic kidney disease

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The role of macrophages in the transition to chronic kidney disease and therapeutic strategies to block this transition are being explored. credit: Chinese Medical Journal

Acute kidney injury (AKI) is a condition in which the kidneys are unable to effectively filter waste products from the blood, causing a variety of health complications. Many studies have shown that acute kidney injury (AKI) subsequently causes long-term kidney injury and progresses to chronic kidney disease (CKD) (more severe renal failure). The transition from AKI to CKD depends on a variety of factors, including sepsis, the type of surgery, and the presence or absence of cardiovascular disease.

Currently, the exact mechanism underlying this multifactorial transition is unknown. Elucidating these mechanisms can contribute to the development of therapeutic strategies to prevent the transition of AKI-CKD. Currently, it is known that macrophages, which are a type of immune cell, play an important role in the transition from AKI to CKD.

To further explore the role of macrophages, a research team led by Dr. Xiaoming Meng of Anhui Medical University in China wrote a review highlighting the effects of various macrophage subtypes on the transition from AKI to CKD.This published article Chinese Medical JournalWe also explored the potential of macrophage-targeted therapies in the prevention of AKI-CKD migration.

The source from which macrophages are derived influences their phenotype and function.In fact, macrophages can evolve into multiple phenotypes, each of which plays a different role in regulation. kidney failure And repair.For example, resident macrophages unique to liver Tissue is involved in anti-inflammatory processes during kidney repair, but circulating macrophages derived from blood monocytes play an pro-inflammatory role as they migrate to the site of injury.

In general, macrophages fall into two types, M1 and M2. Several studies suggest that pro-inflammatory M1 macrophages play a role in certain early processes associated with the development of AKI. On the other hand, M2 macrophages have been shown to reduce AKI-related inflammation and fibrosis.

How do pro-inflammatory macrophages contribute to CKD? “Kidney disorders leading to CKD are enhanced by pro-inflammatory macrophages, which cause the release of some pro-inflammatory cytokines and chemokine, or cause abnormal wound healing processes,” said Dr. Men. It accelerates renal inflammation by ultimately causing renal fibrosis. “

The unique nature of macrophages allows the phenotype to change from M1 to M2 in response to kidney damage. This is a process known as polarization.Macrophages can also alter the renal microenvironment through interaction with Endothelial cells, Immune cells, fibroblasts, and tubular epithelial cells (TEC). For example, macrophages that infiltrate the kidney in response to injury promote TEC damage and death and ultimately block the TEC-induced AKI-CKD translocation.

In sepsis-induced AKI, the cytokine Csf2 secreted by the injured TEC promotes the transition from M1 macrophages to M2 macrophages. Interestingly, certain M2 macrophages expressing the CD206 and / or CD163 receptors contribute to the progression of asymptomatic inflammation, tubular damage, and renal fibrosis. This is in stark contrast to the usual anti-inflammatory effects. In addition, in extreme inflammation, M2 macrophages adopt a “fibrosis-promoting phenotype” to activate myofibroblasts, the cells involved in wound contraction and healing.

“Unexpectedly, we discovered that macrophages can differentiate directly into myofibroblasts through a process known as macrophage-myofibroblast translocation (MMT). These newly formed Myofibroblasts increase renal fibroblasts and ultimately lead to renal failure, “Dr. Meng said. Currently, the exact role of MMT in AKI-CKD migration is unknown.

This article also describes three signaling pathways that contribute to the transition from AKI to CKD, including the Notch signaling pathway, the TGF-β / Smad signaling pathway, and the Wnt / β-catenin signaling pathway. .. “Targeting pathways that regulate macrophage and MMT activation or modification of the macrophage phenotype provides a promising therapeutic approach for kidney disease by blocking the transition from AKI to CKD,” AKI-. Dr. Meng said while discussing ways to prevent CKD migration. ..

Therapeutic strategies that impede macrophage activation and pathogenic roles in this transition have been extensively studied. This article focuses on the role of a molecule known as clodronate liposomes, which can deplete macrophages and reduce the degree of renal fibrosis. Renal fibrosis and subsequent damage can also be prevented by altering macrophage activation and the blocking factors with which they interact.

In addition, treatment with a compound known as quercetin has been shown to block macrophage infiltration and M2 polarization. In addition, a receptor known as colony-stimulating factor (CSF) -1 affects macrophage proliferation, differentiation, and survival. Blocking the gene encoding this receptor can inhibit the growth of macrophages in the kidney.In addition, it has been reported that a molecule known as vorapaxar suppresses it. Macrophages By blocking the pathways involved in the transition from AKI to CKD.

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For more information:
Xiaoming Meng et al, Promoting the Role of Macrophages in the Transition from Acute Kidney Injury to Chronic Kidney Disease, Chinese Medical Journal (2022). DOI: 10.1097 / CM9.0000000000002100

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Quote: The role of macrophages in the progression from acute kidney injury to chronic kidney disease (June 20, 2022) is https: // to 2022 Obtained on June 20, 2014. .html

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The role of macrophages in the progression from acute kidney injury to chronic kidney disease

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