Sirtuin 3 suppresses the formation of renal calcium oxalate crystals through promoting M2 polarization of macrophages

Xi, Junhua; Chen, Yang; Jing, Junfeng; Zhang, Yanbin; Liang, Chaozhao; Hao, Zongyao; Zhang, Li

doi:10.1002/jcp.27803

Cited by 37 publications

(27 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such macrophages have various phenotypes which are influenced by the disease stage, type and microenvironment [39]. Previous studies have identified that genes associated with inflammatory macrophage were upregulation and genes associated with pro-inflammatory macrophage were downregulation [23, 24]. However, the results of their study were not consistent with ours.…”

Section: Discussioncontrasting

confidence: 79%

See 1 more Smart Citation

Landscape of microenvironment in Randall’s plaque by single-cell sequencing

Duan

et al. 2021

Preprint

View full text Add to dashboard Cite

Randall's plaque is significantly associated with the occurrence of nephrolithiasis. However, the microenvironment of Randall's plaque is poorly characterized. To investigate the microenvironment of Randall's plaque, we analyzed single-cell RNA data of 3 Randall's plaque and 3 normal renal papillae tissue and identified 11 different cell types. We screened differentially expressed genes among all cell types between Randall's plaque and normal renal papillae. The microenvironment showed two cell types with multiple stone formation-associated transcriptomic programs. Contrary to previous studies, we did not observe macrophage M1/M2 imbalance. Notably, we detected ossification-associated macrophage is enriched in Randall's plaque and validated GPNMB and ACP5 were potential biomarkers on the ossification-associated macrophage. We also identified an endothelial subset harboring active communication (COL15A1+ PCDH17+ endothelial, DPECs) with other cells. Together with Immunofluorescence, we validated ossification-associated macrophage and DPECs are enriched in Randall's plaque tissue. Finally, cell-to-cell communication revealed that Loop of Henle, DPECs, and osteoblasts-associated macrophages was the main source of SPP1 signaling. Our work will further the understanding of the microenvironment among Randall's plaque tissues and provide deep insight into immune modulation.

show abstract

Section: Discussioncontrasting

confidence: 79%

“…1a ). The alternative (M2) type and classic (M1) type are known to affect RP formation, with M2 having an inhibitory effect on inflammation and reducing effect on CaOx crystal deposition [24]. Macrophages were re-analyzed, yielding 5 clusters ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Landscape of microenvironment in Randall’s plaque by single-cell sequencing

Duan

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Nephrolithiasis is a highly prevalent disease with the incidence of 2–20% in different countries or regions of the world . Calcium oxalate (CaOx) is the most common type of kidney stones, up to 75–90%, and the recurrence rate is approximately 50% within 10 years . The supersaturation, nucleation, growth, aggregation to crystals followed by direct adhesion on renal tubular epithelial cells is the general process of CaOx stones formation in the kidney, further leading to pain, urinary tract infections, chronic renal disease, and even loss of kidney function .…”

Section: Introductionmentioning

confidence: 99%

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Chen

Wei

Meng

et al. 2019

Part & Part Syst Charact

Self Cite

View full text Add to dashboard Cite

Calcium oxalate (CaOx) stone is the most common type of kidney stone, with a formation process comprising supersaturation, nucleation, growth, aggregation to crystals, and adhesion on renal tubular epithelial cells. CaOx stones generally lead to renal injury; however, the underlying mechanism remains poorly understood. Accumulating evidence suggests that nanosized materials could induce much greater toxicity than bulk materials with the same components. As aggregation to nanocrystals is necessary to form CaOx stones and nanocrystals have been widely reported to elicit either prodeath or prosurvival autophagy, the aim is to address the precise role of autophagy in CaOx‐ nanocrystal‐induced cytotoxicity. Clinical CaOx stones from patients are collected followed by ball milling. As a result, CaOx nanocrystals significantly reduce renal cell viability in a dose‐ and time‐dependent manner. Further study shows that CaOx nanocrystals possess an autophagy‐inducing capacity and autophagic flux is complete. Autophagy abrogation by specific chemical inhibitor wortmannin or chloroquine obviously attenuates cytotoxicity, strongly suggesting that prodeath autophagy contributes to CaOx nanocrystals‐elicited cytotoxicity. Finally, it is revealed that autophagy is an essential signaling pathway participating in apoptosis regulation. Collectively, the findings demonstrate the role of autophagy in CaOx‐nanocrystal‐elicited cytotoxicity, and harnessing autophagy can be helpful to design promising strategies for attenuating kidney injury in nephrolithiasis.

show abstract

“…Urinary multiplex comparisons among individuals who did not form stones, and those who formed CaOx stones for the first time and those who formed recurrent CaOx stones, identified IL-1a, IL-1b, IL-4, IL-10, and GM-CSF as potential biomarkers affecting Mφ and neutrophil function in stone development ( 48 ). Furthermore, M1-like Mφ polarization increases pro-inflammatory cytokines such as TNFα, IL-1β, and IL-1, as well as M1/M2-like monocyte ratios in blood samples from patients with CaOx stones compared with those who do not form stones ( 49 ).…”

Section: Resultsmentioning

confidence: 99%

Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature

et al. 2021

View full text Add to dashboard Cite

BackgroundThe global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components in vivo, and in vitro including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy.MethodsWe systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications.ResultsAlthough several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages in vitro and ex vivo showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.ConclusionsThis systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones via crystal phagocytosis.

show abstract

Sirtuin 3 suppresses the formation of renal calcium oxalate crystals through promoting M2 polarization of macrophages

Cited by 37 publications

References 29 publications

Landscape of microenvironment in Randall’s plaque by single-cell sequencing

Landscape of microenvironment in Randall’s plaque by single-cell sequencing

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature

Contact Info

Product

Resources

About