Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway

Huang, Chun‐Kai; Meng, Mingyao; Li, Shuo; Liu, Shiyuan; Li, Lin; Su, Yanjun; Gao, Hui; He, Shan; Zhao, Yiyi; Zhang, Min; Hou, Zhuoni; Wang, Wenju; Wang, Xiaodan

doi:10.3389/fcell.2022.876054

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…In their study, Huang et al (2022) found that levels of TGF-β1 expression in serum and kidney tissues were significantly reduced in a murine lupus nephritis model following treatment with human umbilical cord MSCs, indicating the ability of umbilical MSCs to promote kidney recovery through the TGF-β1 pathway [50]. These data are consistent with the results of our studies on the normalization of TGF-β1 expression levels in an animal model of AKI after the use of human umbilical cord-derived MSCs.…”

Section: а B C Figure 4 -Levels Of Creatinine (A) Urea (B) and Uric A...supporting

confidence: 79%

Morphofunctional changes in the kidneys of rats during acute respiratory distress syndrome and its treatment with human umbilical cord-derived mesenchymal stem cells

Palii,

Dovgalyuk,

Redko

et al. 2024

COT

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Acute respiratory distress syndrome (ARDS) is a severe pathological condition often accompanied by kidney injury. It is known that mesenchymal stem cells (MSCs) have high potential for treating various diseases due to their ability to paracrinely stimulate the regeneration of damaged cells and tissues and restore impaired organ functions. Purpose: To investigate the nephroprotective effect of human umbilical cord MSCs in a model of ARDS induced in rats by intranasal administration of lipopolysaccharide (LPS). Materials and methods: Seventy-two sexually mature male Wistar rats were randomly divided into nine groups: intact animals, 3 days, 7 days, and 28 days of ARDS development, MSC control, and four treatment groups: 24 hours LPS + 2 days MSCs, 4 days LPS + 3 days MSCs, 14 days LPS + 14 days MSCs, 21 days LPS + 7 days MSCs. MSCs were administered intraperitoneally at a dose of 106 cells/kg body weight. Levels of structural kidney damage were assessed using histological analysis of sections stained with hematoxylin and eosin. The expression of the fibrosis marker TGF-β1 in kidney tissues was evaluated by immunohistochemistry technique. Creatinine, urea, and uric acid levels in blood serum were measured using a kinetic method. Results: The conducted studies revealed the presence of significant damage to the kidney parenchyma, signs of fibrosis, and impaired nephron function in rats with modeled ARDS. The severity of pathological changes increased with the duration of the experiment. The use of human umbilical MSCs as a treatment factor significantly reduced the severity of coagulopathy, tubular necrosis, and destruction of renal corpuscles, inhibited the development of interstitial fibrosis, and improved the levels of renal blood markers. The best nephroprotective effect of MSCs was observed on the 28th day of the experiment in the group 14 daysLPS + 14 daysMSCs. This is likely due to the earlier use and longer duration of action of the stem cells compared to the group 21 daysLPS + 7 daysMSCs. Conclusion: Human umbilical MSCs have regenerative, antifibrotic, and nephroprotective effects in an animal model of kidney injury caused by ARDS. This may indicate the therapeutic potential of umbilical MSCs for the treatment of nephropathies of various origins.

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Section: а B C Figure 4 -Levels Of Creatinine (A) Urea (B) and Uric A...supporting

confidence: 79%

Morphofunctional changes in the kidneys of rats during acute respiratory distress syndrome and its treatment with human umbilical cord-derived mesenchymal stem cells

Palii,

Dovgalyuk,

Redko

et al. 2024

COT

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“…Studies have shown that TRAF6 is involved in various kidney diseases. Increased TRAF6 expression has been detected in renal tissues of MRL/Ipr mice (lupus nephritis model) [ 48 ], acute kidney IRI model mice [ 49 ] and LPS-induced podocytes [ 50 ]. However, changes in TRAF6 expression and function in MN have not been studied.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV relieves passive heymann nephritis and podocyte injury by suppressing the TRAF6/NF-κb axis

Ma,

Hu,

Ruan

et al. 2024

Renal Failure

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The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

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“…Immunofluorescence assay evaluated immune complex (total IgG) deposition. HE and Masson scoring was conducted according to previous studies (17)(18)(19). HE staining assessed renal injury from five dimensions, including glomerular injury, tubular injury, renal interstitial inflammation, renal interstitial fibrosis, and protein tubule.…”

Section: Histology and Scoringmentioning

confidence: 99%

GDF-15: A Potential Biomarker and Therapeutic Target in Systemic Lupus Erythematosus

Huang²,

Yang³

et al. 2022

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a rheumatic disease. Growth differentiation factor 15 (GDF-15) is a member of transforming growth factor-β superfamily. To date, association of GDF-15 with SLE pathogenesis is not clarified. This study discussed GDF-15 serum levels and gene polymorphisms in SLE patients and lupus mouse model further demonstrated the role of GDF-15 in lupus development. We conducted two independent case-control studies for SLE patients. One is to evaluate serum levels of GDF-15 in 54 SLE patients and 90 healthy controls, and the other one is to analyze gene polymorphisms of GDF-15 in 289 SLE patients and 525 healthy controls. Serum levels of GDF-15 were detected by ELISA. GDF-15 gene polymorphisms (rs1055150, rs1058587, rs1059519, rs1059369, rs1227731, rs4808793, and rs16982345) were genotyped by the Kompetitive Allele-Specific PCR (KASP) method. Addition of recombinant GDF-15 into pristane-induced lupus mice evaluated histological and serological changes. Results showed that serum levels of GDF-15 were overexpressed in SLE patients and associated with disease activity. Polymorphisms rs1055150, rs1059369, rs1059519, and rs4808793 of GDF-15 gene were related to SLE risk. Lupus mice showed splenomegaly, severe histological scores, and high levels of autoantibodies [antinuclear antibodies (ANA) and total immunoglobulin G (IgG)], whereas administration of GDF-15 into lupus mice reduced the histological changes. Percentages of CD8+, CD11b+, CD19+, CD11C+ cells, TH2 cells, and pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-21, and IL-22) were reduced after GDF-15 treatment in lupus mice. In conclusion, GDF-15 was related to lupus pathogenesis and inhibited lupus development.

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Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway

Cited by 5 publications

References 33 publications

Morphofunctional changes in the kidneys of rats during acute respiratory distress syndrome and its treatment with human umbilical cord-derived mesenchymal stem cells

Morphofunctional changes in the kidneys of rats during acute respiratory distress syndrome and its treatment with human umbilical cord-derived mesenchymal stem cells

Astragaloside IV relieves passive heymann nephritis and podocyte injury by suppressing the TRAF6/NF-κb axis

GDF-15: A Potential Biomarker and Therapeutic Target in Systemic Lupus Erythematosus

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