Single-cell sequencing reveals peritoneal environment and insights into fibrosis in CAPD patients

Wenxue, Hu; Guanglan, Li; Dong, Wei; He, Peng; Liu, Wei; Wu, Yanhua; Huaban, Liang; Feng, Wang; Feng, Yifei; Yin, Yulong; Ye, Zhiming; Wenke, Hao; Liang, Xinling

doi:10.1016/j.isci.2023.106336

Cited by 4 publications

(7 citation statements)

References 62 publications

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“…43,44 In patients with peritoneal fibrosis, peritoneal macrophages change their heterogeneity and participate in the fibrotic reaction. 44 In a cancer metastasis model, PPARγ activation by a drug was shown to drive differentiation of SPMs to LPMs in the peritoneal cavity and suppress tumor growth indirectly. 45 Our study showed that LPMs lose their phenotypes and acquire an inflammatory phenotype in capsular fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

Balog,

Jeong,

Asahina

2023

The FASEB Journal

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Upon injury to Glisson's capsule, mesothelial cells covering the liver surface differentiate into myofibroblasts and participate in capsular fibrosis. In the fibrotic area, infiltrating macrophages are present, but their origin and role in capsular fibrosis remain elusive. In the present study, we examined whether macrophages in the peritoneal cavity migrate to the liver and participate in capsular fibrosis. Capsular fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. Chlorhexidine gluconate treatment induced disappearance of CD11bHigh F4/80High large peritoneal macrophages from the peritoneal cavity. Transplantation of TIMD4+ large peritoneal macrophages to the mouse peritoneal cavity resulted in their recruitment to the fibrotic area of the liver. Bone marrow‐derived monocytes were also recruited to the chlorhexidine gluconate‐induced fibrotic area upon their transplantation to the peritoneal cavity. However, bone marrow‐derived macrophages, Kupffer cells, peritoneal B cells, and small peritoneal macrophages prepared from chlorhexidine gluconate‐treated mice did not exhibit such potential. In the hepatic fibrotic area, peritoneal macrophages lost expression of unique markers (Gata6, Timd4) and increased expression of genes involved in inflammation (Il1b, Il6, Tnf) and extracellular matrix remodeling (Mmp13, Timp1). Depletion of peritoneal macrophages by clodronate liposomes reduced capsular fibrosis. Our data indicate that large peritoneal macrophages are recruited to the injured liver surface and promote capsular fibrosis by inducing inflammation and extracellular matrix remodeling. Modulating the function of peritoneal macrophages might be a new approach for suppressing capsular fibrosis.

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Section: Discussionmentioning

confidence: 99%

“…Recent studies using single‐cell RNA sequencing revealed heterogeneity of macrophages in the human peritoneal cavity 43,44 . In patients with peritoneal fibrosis, peritoneal macrophages change their heterogeneity and participate in the fibrotic reaction 44 .…”

Section: Discussionmentioning

confidence: 99%

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

Balog,

Jeong,

Asahina

2023

The FASEB Journal

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“…Second, genes had to be expressed in more than 25% of the cells belonging to the target cluster. Third, a P value is less than 0.05 ( 88 ).…”

Section: Methodsmentioning

confidence: 99%

col1a2 ⁺ fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish

Chen,

Wang,

et al. 2024

Sci. Adv.

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Animals evolve diverse pigment patterns to adapt to the natural environment. Countershading, characterized by a dark-colored dorsum and a light-colored ventrum, is one of the most prevalent pigment patterns observed in vertebrates. In this study, we reveal a mechanism regulating xanthophore countershading in zebrafish embryos. We found that csf1a and csf1b mutants altered xanthophore countershading differently: csf1a mutants lack ventral xanthophores, while csf1b mutants have reduced dorsal xanthophores. Further study revealed that csf1a is expressed throughout the trunk, whereas csf1b is expressed dorsally. Ectopic expression of csf1a or csf1b in neurons attracted xanthophores into the spinal cord. Blocking csf1 signaling by csf1ra mutants disrupts spinal cord distribution and normal xanthophores countershading. Single-cell RNA sequencing identified two col1a2 + populations: csf1a high csf1b high muscle progenitors and csf1a high csf1b low fibroblast progenitors. Ablation of col1a2 + fibroblast and muscle progenitors abolished xanthophore patterns. Our study suggests that fibroblast and muscle progenitors differentially express csf1a and csf1b to modulate xanthophore patterning, providing insights into the mechanism of countershading.

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“…PMCs originate from mesoderm and can differentiate into fibroblasts under external stimuli. 5 PMCs undergoing the MMT process possess the ability to secrete cytokines, collagen, and proteoglycans to participate in the remodeling of the extracellular matrix. Thus, inhibiting the MMT process of PMCs is significant for the long-term clinical application of PD.…”

Section: Introductionmentioning

confidence: 99%

“…Yet there is no effective preventive or therapeutic approach. PMCs originate from mesoderm and can differentiate into fibroblasts under external stimuli 5 . PMCs undergoing the MMT process possess the ability to secrete cytokines, collagen, and proteoglycans to participate in the remodeling of the extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

SPHK1/S1P/S1PR pathway promotes the progression of peritoneal fibrosis by mesothelial‐mesenchymal transition

Zhao,

Ding,

Sun

et al. 2024

The FASEB Journal

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Long‐term exposure to non‐physiologically compatible dialysate inevitably leads to peritoneal fibrosis (PF) in patients undergoing peritoneal dialysis (PD), and there is no effective prevention or treatment for PF. Sphingosine‐1‐phosphate (S1P) is a bioactive sphingolipid produced after catalysis by sphingosine kinase (SPHK) 1/2 and activates signals through the S1P receptor (S1PR) via autocrine or paracrine. However, the role of SPHK1/S1P/S1PR signaling has never been elucidated in PF. In our research, we investigated S1P levels in peritoneal effluents and demonstrated the role of SPHK1/S1P/S1PR pathway in peritoneal fibrosis. It was found that S1P levels in peritoneal effluents were positively correlated with D/P Cr (r = 0.724, p < .001) and negatively correlated with 4 h ultrafiltration volume (r = −0.457, p < .001). S1PR1 and S1PR3 on peritoneal cells were increased after high glucose exposure in vivo and in vitro. Fingolimod was applied to suppress S1P/S1PR pathway. Fingolimod restored mouse peritoneal function by reducing interstitial hyperplasia, maintaining ultrafiltration volume, reducing peritoneal transport solute rate, and mitigating the protein expression changes of fibronectin, vimentin, α‐SMA, and E‐cadherin induced by PD and S1P. Fingolimod preserved the morphology of the human peritoneal mesothelial cells, MeT‐5A, and moderated the mesothelial‐mesenchymal transition (MMT) process. We further delineated that SPHK1 was elevated in peritoneal cells after high glucose exposure and suppression of SPHK1 in MeT‐5A cells reduced S1P release. Overexpression of SPHK1 in MeT‐5A cells increased S1P levels in the supernatant and fostered the MMT process. PF‐543 treatment, targeting SPHK1, alleviated deterioration of mouse peritoneal function. In conclusion, S1P levels in peritoneal effluent were correlated with the deterioration of peritoneal function. SPHK1/S1P/S1PR pathway played an important role in PF.

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Single-cell sequencing reveals peritoneal environment and insights into fibrosis in CAPD patients

Cited by 4 publications

References 62 publications

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

col1a2 ⁺ fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish

SPHK1/S1P/S1PR pathway promotes the progression of peritoneal fibrosis by mesothelial‐mesenchymal transition

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Single-cell sequencing reveals peritoneal environment and insights into fibrosis in CAPD patients

Cited by 4 publications

References 62 publications

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

col1a2 + fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish

SPHK1/S1P/S1PR pathway promotes the progression of peritoneal fibrosis by mesothelial‐mesenchymal transition

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col1a2 ⁺ fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish