The KCa3.1 blocker TRAM-34 inhibits proliferation of fibroblasts in paraquat-induced pulmonary fibrosis

Xie, Hui; Lü, Jian; Zhu, Yong; Meng, Xiaoxiao; Wang, Ruilan

doi:10.1016/j.toxlet.2018.07.020

Cited by 11 publications

(2 citation statements)

References 32 publications

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“…By contrast, in pathological conditions, K Ca 3.1 channels control fibrosis in several tissues [22]. For example, the block of K Ca 3.1 channels is evaluated as a possible treatment of fibrosis in tissues as diverse as cornea [23], kidney [24], vasculature [25] and lung [26]. In the heart, blockade of K Ca 3.1 channels prevents myocardial fibrosis in models of hypertension [27,28].…”

Section: Introductionmentioning

confidence: 99%

Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels

Morotti

Garofalo

Cocozza

et al. 2022

Life

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Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (KCa3.1) plays key roles in controlling both macrophage phenotype and fibroblast proliferation, two critical contributors to muscle damage. In this work, we demonstrate that pharmacological blockade of the channel in the mdx mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in muscles, with a concomitant reduction of muscle damage. As already observed with other treatments, no improvement in muscle performance was observed in vivo. In conclusion, this work supports the idea that KCa3.1 channels play a contributing role in controlling damage-causing cells in DMD. A more complete understanding of their function could lead to the identification of novel therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels

Morotti

Garofalo

Cocozza

et al. 2022

Life

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“…The same observation was found in one previous study of pulmonary fibrosis in rats. The expression of TGF-β1 in rat's lung tissues in that study were not affected by TRAM-34 (Xie et al, 2018).. However, there is no obvious evidence of role of KCa3.1 about fibrotic disease in feline species via TGF-β/Smad signaling.…”

Section: Chapter V Discussionmentioning

confidence: 61%

Role of KCa3.1 channel on renal fibrosis in Doxorubicin-induced feline kidney cell line

Kuedbantakien

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Feline renal fibrosis is the most common outcome of chronic kidney disease in cats. Nowadays, there is no specific treatment and the mechanism of fibrosis in cats is still unknown. Intermediate conductance Ca2+ activated K+ channel (KCa3.1) plays an important role in novel therapy for organ fibrosis in many species. Transforming growth factor- ? (TGF-?)/Smad signaling pathway and KCa3.1 has been shown to relate to renal fibrosis. This study aimed to investigate the relationship between KCa3.1 and feline renal fibrosis via TGF-?/Smad signaling pathway. CRFK cultures were induced with doxorubicin (DOX) to generate feline renal fibrosis model. Triarymethane-34 (TRAM-34), selective inhibitor of KCa3.1 was used for blocking KCa3.1 function pretreatment before fibrosis induction. TGF-? receptor type 2 (TGF-?R2), Smad2/3, ?-Smooth muscle actin (?-SMA) which are fibrotic markers in TGF-?/Smad signaling cascade were measured using western blot to compare the fibrosis production between the normal KCa3.1 expression and KCa 3.1 blockage CRFK cells. The cell viability assay was performed alongside with protein expression measurement. CRFK cells pretreatment with TRAM-34 before DOX induction has no significant difference of percentage of cell viability when compared to negative control group. CRFK with DOX incubation alone significantly declined the percentage of cell viability compared to negative control (p<0.05). Interestingly, the expression of TGF-?R2 and Smad2/3 were not significant difference when compared between all study groups but ?-SMA level in DOX induction group with and without TRAM-34 pretreatment were significant decrease when compared to negative control group (p<0.05). These findings indicated that KCa3.1 may not be involved in fibrogenesis in feline kidney cells via TGF-?/Smad signaling pathway and DOX may affect to ?-SMA production in CRFK cells. The further investigation of KCa3.1 in feline renal fibrosis on another fibrotic partway is needed to be evaluated in the future.

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MiR-506-3p suppresses the proliferation of ovarian cancer cells by negatively regulating the expression of MTMR6

et al. 2019

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The KCa3.1 blocker TRAM-34 inhibits proliferation of fibroblasts in paraquat-induced pulmonary fibrosis

Cited by 11 publications

References 32 publications

Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels

Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels

Role of KCa3.1 channel on renal fibrosis in Doxorubicin-induced feline kidney cell line

MiR-506-3p suppresses the proliferation of ovarian cancer cells by negatively regulating the expression of MTMR6

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