SIRT1-modified human umbilical cord mesenchymal stem cells ameliorate experimental peritoneal fibrosis by inhibiting the TGF-β/Smad3 pathway

Guo, Yanhong; Wang, Liuwei; Gou, Rong; Wang, Yulin; Shi, Xiujie; Pang, Xinxin; Tang, Lin

doi:10.1186/s13287-020-01878-2

Cited by 13 publications

(9 citation statements)

References 42 publications

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“…Previous studies have revealed that the signaling pathways involved in peritoneal fibrosis are very complex, mainly including the cannabinoid signaling pathway, oxidative stress signaling pathway, TGF-β signaling pathway, NF-kB signaling pathway, Sonic Hedgehog signaling pathway, etc. [ 23 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative role of SIRT1 in peritoneal fibrosis: an in vivo and in vitro study

et al. 2021

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Background Peritoneal fibrosis is one of the major complications induced by peritoneal dialysis (PD). Damaged integrity and function of peritoneum caused by peritoneal fibrosis not only limits the curative efficacy of PD and but affects the prognosis of patients. However, the detailed mechanisms underlying the process remain unclear and therapeutic strategy targeting TGF‐β is deficient. Transforming growth factor‐β (TGF‐β) signaling participates in the progression of peritoneal fibrosis through enhancing mesothelial-mesenchymal transition of mesothelial cells. Methods The study aims to demonstrate the regulatory role of Sirtuin1 (SIRT1) to the TGF‐β signaling mediated peritoneal fibrosis. SIRT1−/− mice were used to establish animal model. Masson’s staining and peritoneal equilibration assay were performed to evaluate the degree of peritoneal fibrosis. QRT-PCR assays were used to estimate the RNA levels of Sirt1 and matrix genes related to peritoneal fibrosis, and their protein levels were examined by Western blot assays. Results SIRT1 significantly decreased in vivo post PD treatment. SIRT1 knockout exacerbated peritoneal fibrosis both in vivo and vitro. Overexpression of SIRT1 efficiently inhibited peritoneal fibrosis by inhibiting the peritoneal inflammation and the activation of TGF‐β signaling. Conclusion SIRT1 ameliorated peritoneal fibrosis both in vivo and in vitro through inhibiting the expression of protein matrix induced by TGF‐β signaling.

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Section: Discussionmentioning

confidence: 99%

Ameliorative role of SIRT1 in peritoneal fibrosis: an in vivo and in vitro study

et al. 2021

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“…Subjects in the control, NaCl and Mannitol groups were intraperitoneally injected with a volume of 25 ml twice daily for 6 weeks. Animals in the PD group were injected continuously for 3 days starting on the second week, with a daily dose of 4.25% PD solution containing 0.5% lipopolysaccharide (50 ml) to promote peritoneal fibrosis 22 . Rats in the AAV group were injected with Adeno-associated virus (AAV) after 2 weeks, and each rat was intraperitoneally injected with 2×10 10 viral genomes.…”

Section: Methodsmentioning

confidence: 99%

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis

Li,

Zhang,

Che

et al. 2024

Int. J. Med. Sci.

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Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

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“…4.25% HGPDS or PBS was intraperitoneally injected daily into male mice for 4 weeks. The peritoneal equilibration test (PET) was conducted 28 days after PD treatment as previously described [20, 21]. The dialysate creatinine concentration (D), plasma creatinine concentration (P), peritoneal fluid glucose concentration (D0), and peritoneal fluid glucose concentration (D2) were measured.…”

Section: Methodsmentioning

confidence: 99%

Loss of JNK-Associated Leucine Zipper Protein Promotes Peritoneal Dialysis-Related Peritoneal Fibrosis

et al. 2022

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Background: Peritoneal dialysis-related peritoneal fibrosis is the leading cause of peritoneal ultrafiltration failure. Multitude factors and pathological processes have been implicated in peritoneal fibrosis development and progression, whereas the intrinsic anti-fibrotic mechanism has rarely been explored. JNK-associated leucine zipper protein (JLP) has been recently found possessing powerful anti-fibrotic merits of overall antagonizing TGF-β-induced profibrotic effects. Objectives: We wondered whether JLP is expressed in the peritoneum, and if so, whether it exerts the anti-fibrotic effects similar to those in the kidney. Method: Here, we examined and confirmed JLP expression in peritoneum tissue of mice. Then, we established a peritoneal fibrosis model in Jlp wild-type and Jlp global deficient mice and observed the different effects of Jlp on peritoneal fibrosis progression. In vitro studies were performed on peritoneal mesothelial HMrSV5 cells with or without Jlp knockdown to investigate the underlying mechanism by which Jlp exerts anti-fibrotic effects. Results: We found that the expression of JLP decreased in a high-glucose peritoneal dialysis solution (HGPDS)-induced peritoneal fibrosis mouse model and in HGPDS-treated peritoneal mesothelial cell HMrSV5. JLP deletion exacerbated HGPDS-induced peritoneal fibrosis in peritoneal fibrosis mice, and knockdown of JLP resulted in an increased profibrotic response to HGPDS stimulation in HMrSV5 cells, which was associated with epithelial-to-mesenchymal transition, elevated autophagy, and apoptosis, as well as enhanced TGF-β1/Smad signaling activation. Conclusions: Our findings revealed a new anti-fibrotic factor of Jlp involved in peritoneal fibrosis induction and shed light on novel therapeutic targets in peritoneal ultrafiltration failure.

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SIRT1-modified human umbilical cord mesenchymal stem cells ameliorate experimental peritoneal fibrosis by inhibiting the TGF-β/Smad3 pathway

Cited by 13 publications

References 42 publications

Ameliorative role of SIRT1 in peritoneal fibrosis: an in vivo and in vitro study

Ameliorative role of SIRT1 in peritoneal fibrosis: an in vivo and in vitro study

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis

Loss of JNK-Associated Leucine Zipper Protein Promotes Peritoneal Dialysis-Related Peritoneal Fibrosis

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