Hirudin, a thrombin inhibitor, attenuates TGF-β-induced fibrosis in renal proximal tubular epithelial cells by inhibition of protease-activated receptor 1 expression via S1P/S1PR2/S1PR3 signaling

Lin, Qiang; Long, Chunli; Wang, Zhengang; Wang, Ronghui; Shi, Wei; Qiu, Jiwei; Mo, Junlin; Xie, Yongxiang

doi:10.3892/etm.2021.10924

Cited by 9 publications

(9 citation statements)

References 31 publications

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“…In vivo/ In vitro (16) confirmed in renal biopsy specimens of DN patients, specifically in the glomeruli and interstitium (24). Levels of IL-6 in serum and urinary have emerged as potential markers for DN (25).…”

Section: Uuo Mice and Tgf-binduced Hk-2 Cellsmentioning

confidence: 87%

“…Moreover, hirudin suppresses the expression of inflammatory factors, fibrotic proteins, and ECM in UUO mice, thus counteracting renal fibrosis (15). In the HK-2 cells and renal tissues of UUO mice, hirudin weakens the upregulation of PAR1, S1PR2, and S1PR3 mediated by TGF-b and downregulates the S1P/ S1PR1/S2PR1 signaling-mediated PAR3, diminishing EMT, fibrosis, and MCP-1 expression in HK-2 cells induced by TGF-b (16). The fibre-promoting effects of TGF-b are shown in Figure 1 and hirudin inhibits expression of TGF-b.…”

Section: Inhibition Of Renal Fibrosismentioning

confidence: 99%

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Research progress on the treatment of diabetic nephropathy with leech and its active ingredients

Tian,

Yi,

Yang

et al. 2024

Front. Endocrinol.

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Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy.

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Section: Uuo Mice and Tgf-binduced Hk-2 Cellsmentioning

confidence: 87%

Section: Inhibition Of Renal Fibrosismentioning

confidence: 99%

Research progress on the treatment of diabetic nephropathy with leech and its active ingredients

Tian,

Yi,

Yang

et al. 2024

Front. Endocrinol.

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“…(b) Its regulation was reported to depend on Smad3, mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways [ 44 , 57 ]. (c) TGF-β significantly increases PAR1 expression via the S1P/S1PR2/S1PR3 signaling pathway in regulating expressions of fibrosis- and epithelial-mesenchymal transition (EMT)-related proteins [ 58 ]. We found that TGF-β-mediated PAR1 upregulation is not only time but also tumor cell dosage dependent.…”

Section: Discussionmentioning

confidence: 99%

Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer

Hung,

Fan,

Wang

et al. 2023

BMC Med

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Background Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year survival rate of 6% following a diagnosis, and novel therapeutic modalities are needed. Protease-activated receptor 1 (PAR1) is abundantly overexpressed by both tumor cells and multiple stroma cell subsets in the tumor microenvironment (TME), thereby offering a suitable immunotherapy target. Methods A chimeric antigen receptor (CAR) strategy was applied to target PAR1 using a human anti-PAR1 scFv antibody fused to the transmembrane region with two co-stimulatory intracellular signaling domains of cluster of differentiation 28 (CD28) and CD137 (4-1BB), added to CD3ζ in tandem. Results The engineered PAR1CAR-T cells eliminated PAR1 overexpression and transforming growth factor (TGF)-β-mediated PAR1-upregulated cancer cells by approximately 80% in vitro. The adoptive transfer of PAR1CAR-T cells was persistently enhanced and induced the specific regression of established MIA PaCa-2 cancer cells by > 80% in xenograft models. Accordingly, proinflammatory cytokines/chemokines increased in CAR-T-cell-treated mouse sera, whereas Ki67 expression in tumors decreased. Furthermore, the targeted elimination of PAR1-expressing tumors reduced matrix metalloproteinase 1 (MMP1) levels, suggesting that the blocking of the PAR1/MMP1 pathway constitutes a new therapeutic option for PDAC treatment. Conclusions Third-generation PAR1CAR-T cells have antitumor activity in the TME, providing innovative CAR-T-cell immunotherapy against PDAC.

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“…Hirudin can improve RIF and has many advantages, including safety and low cost, which has attracted the attention of many researchers. Hirudin can inhibit inflammation and reduce the activation of the TGF-β pathway, thereby inhibiting EMT and improving RIF ( Xie et al, 2020 ; Lin et al, 2022 ).…”

Section: Mechanisms Of Rif Interventionmentioning

confidence: 99%

Research Progress of Chinese Herbal Medicine Intervention in Renal Interstitial Fibrosis

et al. 2022

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Chronic kidney diseases usually cause renal interstitial fibrosis, the prevention, delay, and treatment of which is a global research hotspot. However, no definite treatment options are available in modern medicine. Chinese herbal medicine has a long history, rich varieties, and accurate treatment effects. Hitherto, many Chinese herbal medicine studies have emerged to improve renal interstitial fibrosis. This paper reviews the mechanisms of renal interstitial fibrosis and recent studies on the disease intervention with Chinese herbal medicine through literature search, intend to reveal the importance of Chinese herbal medicine in renal interstitial fibrosis. The results show that Chinese herbal medicine can improve renal interstitial fibrosis, and the effects of Chinese herbal medicine on specific pathological mechanisms underlying renal interstitial fibrosis have been explored. Additionally, the limitations and advantages of Chinese herbal medicine in the treatment of renal interstitial fibrosis, possible research directions, and new targets of Chinese herbal medicine are discussed to provide a basis for studies of renal interstitial fibrosis.

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Hirudin, a thrombin inhibitor, attenuates TGF-β-induced fibrosis in renal proximal tubular epithelial cells by inhibition of protease-activated receptor 1 expression via S1P/S1PR2/S1PR3 signaling

Cited by 9 publications

References 31 publications

Research progress on the treatment of diabetic nephropathy with leech and its active ingredients

Research progress on the treatment of diabetic nephropathy with leech and its active ingredients

Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer

Research Progress of Chinese Herbal Medicine Intervention in Renal Interstitial Fibrosis

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