M2 macrophages in kidney disease: biology, therapies, and perspectives

Chen, Titi; Cao, Qi; Wang, Yiping; Harris, David C.H.

doi:10.1016/j.kint.2018.10.041

Cited by 133 publications

(117 citation statements)

References 160 publications

(191 reference statements)

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…The macrophages exhibit a spectrum of activated phenotypes rather than discrete stable subpopulations. The M1 and M2 macrophages represent two extreme phenotypic spectra with a continuum of intermediate phenotypes between M1 and M2 phenotypes . The macrophages are reported to have pathogenic roles in human kidney diseases.…”

Section: Introductionmentioning

confidence: 99%

“…The M1 and M2 macrophages represent two extreme phenotypic spectra with a continuum of intermediate phenotypes between M1 and M2 phenotypes. 10 The macrophages are reported to have pathogenic roles in human kidney diseases. After AKI, the neutrophils and natural killer cells are recruited to the damaged renal tissue within hours, which is followed by the infiltration of inflammatory monocytes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury

Mao

Wang

Zhang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a clinical condition that is associated with high morbidity and mortality. Inflammation is reported to play a key role in AKI. Although the M2 macrophages exhibit antimicrobial and anti‐inflammatory activities, their therapeutic potential has not been evaluated for AKI. This study aimed to investigate the protective effect of peritoneal M2 macrophage transplantation on AKI in mice. The macrophages were isolated from peritoneal dialysates of mice. The macrophages were induced to undergo M2 polarization using interleukin (IL)‐4/IL‐13. AKI was induced in mice by restoring the blood supply after bilateral renal artery occlusion for 30 minutes. The macrophages were injected into the renal cortex of mice. The changes in renal function, inflammation and tubular proliferation were measured. The M2 macrophages were co‐cultured with the mouse primary proximal tubular epithelial cells (PTECs) under hypoxia/reoxygenation conditions in vitro. The PTEC apoptosis and proliferation were analysed. The peritoneal M2 macrophages effectively alleviated the renal injury and inflammatory response in mice with ischaemia‐reperfusion injury (IRI) and promoted the PTEC proliferation in vivo and in vitro. These results indicated that the peritoneal M2 macrophages ameliorated AKI by decreasing inflammatory response and promoting PTEC proliferation. Hence, the peritoneal M2 macrophage transplantation can serve as a potential cell therapy for renal diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury

Mao

Wang

Zhang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Increased numbers of M2 than M1 macrophages have been found in some studies to correlate with graft-loss [99]. KLF4 expression in increased in the InstaScore, and interestingly this gene plays a key role to polarize macrophage into the M2 subset [100], which undertake host defense and wound healing/tissue remodeling tasks [101] and thus can be found to be enriched in renal fibrosis [102].In the AR bopsies in this study, as expected, M1 macrophage signatures were higher in AR [103]. Thus, the macrophage subsets show a dynamic state of skewing the preponderance of M2 to M1 macrophages in the process of immunological priming from pre-AR and full blown AR, and the InstaScore uncovers the state of AR priming or pre-AR in histologically and clinically stable kidney transplants, further highlighting the value of identifying hSTA grafts that are thus at greater risk of AR over time.…”

Section: Discussionmentioning

confidence: 97%

Precision Sub-phenotyping of Histologically Stable Kidney Transplants by a Composite Molecular and Cellular Instability Score

Rychkov

S²,

Sirota

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Initially during renal damage, macrophages can acquire a phenotype known as M1 (iNOS+/CD80+/CCR7+) which favors a pro-inflammatory microenvironment [66]. On the other hand, as the kidney disease progresses, these macrophages polarize to M2 (CD86-/CD163+/CD206+) which have an anti-inflammatory role promoting the healing of damaged tissue and are therefore considered pro-fibrotic [66,68]. This is why macrophage infiltration has been studied in different glomerular pathologies, proposing that glomerulus cells deliver chemoattractant chemokines which also promote the expression of cell adhesion molecules in macrophages [69][70][71][72].…”

Section: Discussionmentioning

confidence: 99%

Intraglomerular Monocyte/Macrophage Infiltration and Macrophage–Myofibroblast Transition during Diabetic Nephropathy Is Regulated by the A2B Adenosine Receptor

Torres

Muñoz

Nahuelpán

et al. 2020

Cells

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is considered the main cause of kidney disease in which myofibroblasts lead to renal fibrosis. Macrophages were recently identified as the major source of myofibroblasts in a process known as macrophage-myofibroblast transition (MMT). Adenosine levels increase during DN and in vivo administration of MRS1754, an antagonist of the A 2B adenosine receptor (A 2B AR), attenuated glomerular fibrosis (glomerulosclerosis). We aimed to investigate the association between A 2B AR and MMT in glomerulosclerosis during DN. Kidneys/glomeruli of non-diabetic, diabetic, and MRS1754-treated diabetic (DM+MRS1754) rats were processed for histopathologic, transcriptomic, flow cytometry, and cellular in vitro analyses. Macrophages were used for in vitro cell migration/transmigration assays and MMT studies. In vivo MRS1754 treatment attenuated the clinical and histopathological signs of glomerulosclerosis in DN rats. Transcriptomic analysis demonstrated a decrease in chemokine-chemoattractants/cell-adhesion genes of monocytes/macrophages in DM+MRS1754 glomeruli. The number of intraglomerular infiltrated macrophages and MMT cells increased in diabetic rats. This was reverted by MRS1754 treatment. In vitro cell migration/transmigration decreased in macrophages treated with MRS1754. Human macrophages cultured with adenosine and/or TGF-β induced MMT, a process which was reduced by MRS1754. We concluded that pharmacologic blockade of A 2B AR attenuated some clinical signs of renal dysfunction and glomerulosclerosis, and decreased intraglomerular macrophage infiltration and MMT in DN rats.Cells 2020, 9, 1051 2 of 21 that affects close to 50% of patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) [3,7]. During DN, patients lose glomerular function. This is clinically manifested by the appearance of proteins in the urine (proteinuria; an albumin excretion rate ≥300 mg/24 h per gram of creatinine) and/or a reduced glomerular filtration rate (GFR; below 60 mL/min/1.73 m 2 ) [2]. In addition, people with DN who reach the stage of CKD [8] show an increase in the production of urine (polyuria), the appearance of glucose in the urine (glycosuria), and an increase in blood urea nitrogen (BUN) and serum creatinine [9]. Currently, management of DN patients involves the use of antihypertensive, antidyslipidemic, and antidiabetic agents, however these drugs have only shown a modest efficacy in slowing the evolution of the disease [10]. Regardless of the treatment used, the progression of DN leads to renal fibrosis [11], which irreversibly remodels the parenchyma tissue replacing it with extracellular matrix (ECM), thereby losing functionality [12]. Renal fibrosis predisposes patients to organ replacement therapies, such as hemodialysis and kidney transplantation, which means serious economic and societal costs for health systems [1,2,[13][14][15]. The pathophysiological events that trigger renal fibrosis are still unknown, however, this process is orchestrated by myofibroblasts, cells which have the ca...

show abstract

M2 macrophages in kidney disease: biology, therapies, and perspectives

Cited by 133 publications

References 160 publications

Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury

Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury

Precision Sub-phenotyping of Histologically Stable Kidney Transplants by a Composite Molecular and Cellular Instability Score

Intraglomerular Monocyte/Macrophage Infiltration and Macrophage–Myofibroblast Transition during Diabetic Nephropathy Is Regulated by the A2B Adenosine Receptor

Contact Info

Product

Resources

About