Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by TGF-β1

Guo, Yuanyuan; Dong, Zengxiang; Shi, Yuanqi; Wang, Wei; Wang, Lu; Sun, Jing; Sun, Xin; Tian, Zhen; Yao, Jianting; Li, Zhitao; Cheng, Jiali; Tian, Ye

doi:10.1159/000452571

Cited by 17 publications

(12 citation statements)

References 30 publications

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“…The precise mechanisms responsible for the actions of these inhibitors require further investigation. Further, we evaluated the effects of T16Ainh-A01 and CaCCinh-A01 on the expression of α-SMA, a typical marker of myofibroblasts, which are closely associated with cardiac fibrosis [30,31], and demonstrated that both inhibitors reduced α-SMA expression at the mRNA and protein level. The synthesis and secretion of collagen are the main functions of CFs, which play a pivotal role in the myocardial repair process [32].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Effects of the Calcium-Activated Chloride Channel Inhibitors T16Ainh-A01 and CaCCinh-A01 on Cardiac Fibroblast Function

Tian

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Calcium-activated chloride channels (CaCCs) regulate numerous physiological processes including cell proliferation, migration, and extracellular matrix secretion. T16Ainh-A01 and CaCCinh-A01 are selective inhibitors of CaCCs. But it is unknown whether these two compounds have functional effects on cardiac fibroblasts (CFs). Methods: Primary CFs were obtained by enzymatic dissociation of cardiomyocytes from neonatal rat hearts. Intracellular Ca²⁺ ([Ca²⁺]_i) and Cl^- ([Cl^-]_i) were measured using the fluorescent calcium indicators (Fluo-4 AM) and N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide respectively. The expression of anoctamin-1 (ANO1) and α-smooth muscle actin (α-SMA) was detected by quantitative RT-PCR, immunofluorescence, and western blotting. A hydroxyproline assay was used to examine collagen secretion. Cell proliferation, cell cycle distribution, and cell migration were assessed by Cell Counting Kit-8, flow cytometry, and Transwell assays, respectively. Results: ANO1 was preferentially expressed on the nuclear membrane and partially within intracellular compartments around the nucleus. T16Ainh-A01 and CaCCinh-A01 displayed different inhibitory effects on [Cl^-]_i in CFs. T16Ainh-A01 considerably decreased [Cl^-]_i in the nucleus, whereas CaCCinh-A01 reduced [Cl^-]_i in intracellular compartments around the nucleus, and both inhibitors exhibited a minimal effect on [Ca²⁺]_i in CFs. ANO1 and α-SMA expression levels were significantly repressed by CaCCinh-A01. T16Ainh-A01 showed a marked inhibitory effect on the mRNA levels of ANO1 and α-SMA, but had a negligible effect on ANO1 at the protein level. T16Ainh-A01 and CaCCinh-A01 led to the significant repression of cell proliferation, cell migration, and collagen secretion in CFs. Conclusion: Our findings indicate that T16Ainh-A01 and CaCCinh-A01 have the potential to inhibit the proliferation and collagen secretion of CFs and may serve as novel anti-fibrotic therapeutic drugs in the future.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Effects of the Calcium-Activated Chloride Channel Inhibitors T16Ainh-A01 and CaCCinh-A01 on Cardiac Fibroblast Function

Tian

Wang

et al. 2018

Cell Physiol Biochem

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“…Furthermore, our data suggested that HP also affects Akt signaling in HCFs. Therefore, we focused on the phosphorylation of Akt (Ser473) among the proteins we evaluated, because phosphorylation of Akt, which is involved in cardiac fibrotic changes, was highly increased in our study (Villarreal et al 2009;Guo et al 2016;Phosri et al 2017).…”

Section: Resultsmentioning

confidence: 99%

Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts

et al. 2018

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Mechanical stresses play important roles in the process of constructing and modifying heart structure. It has been well established that stretch force acting on cardiac fibroblasts induces fibrosis. However, the effects of compressive force, that is, hydrostatic pressure (HP), have not been well elucidated. We thus evaluated the effects of HP using a pressure‐loading apparatus in human cardiac fibroblasts (HCFs) in vitro. In this study, high HP (200 mmHg) resulted in significant phosphorylation of Akt in HCFs. HP then greatly inhibited glycogen synthase kinase 3 (GSK‐3)α, which acts downstream of the PI3K/Akt pathway. Similarly, HP suppressed mRNA transcription of inflammatory cytokine‐6, collagen I and III, and matrix metalloproteinase 1, compared with an atmospheric pressure condition. Furthermore, HP inhibited collagen matrix production in a three‐dimensional HCF culture. Taken together, high HP suppressed the differentiation of fibroblasts into the myofibroblast phenotype. HP under certain conditions suppressed cardiac fibrosis via Akt/GSK‐3 signaling in HCFs. These results might help to elucidate the pathology of some types of heart disease.

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“…Dehner et al, 2008;Lang and Stournaras, 2013;Sahin et al, Giebisch, 1998;Arteaga and Canessa, 2005;Seebohm et al, 2005;Lang et al, 2006;Lang and Shumilina, 2013. Carriers and pumps Na + ,K + ,2Cl − cotransporters (NKCC2), NaCl cotransporter (NCC), Na + /H + exchangers (NHE1, NHE3), facilitative (GLUT1, GLUT4), Na + -coupled (SGLT1) glucose transporters, amino acid (ASCT2, SN1, B(0)AT1, EAAT1, EAAT2, EAAT3, EAAT4, EAAT5) peptide (PepT) transporters, Na + ,dicarboxylate cotransporter (NaDC-1), creatine transporter (CreaT), Na + ,myoinositol cotransporter (SMIT), phosphate carriers (NaPiIIa, NaPiIIb), Na + /K + -ATPase, albumin uptake Lang et al, 2006. Lang et al, 2006Lang and Stournaras, 2013. Signaling molecules etc., nephrin, type A natriuretic peptide receptor (NPR-A), Ca 2+ -regulated heat-stable protein of apparent molecular mass 24 kDa (CRHSP24), adaptor precursor (APP) Fe65, NDRG1 and NDRG2, myosin-Vc, filamin C, microtubule-associated protein tau, Cyclin-dependent kinase inhibitor 1B (p27 Kip1 ), huntingtin McCaig et al, 2011;Ohashi et al, 2011;Lang and Stournaras, 2013;Sahin et al, 2013;Voelkl et al, 2015;Lang et al, 2018. SGK1 expression is enhanced by TGF-β which is a stimulator of fibrosis (Akhurst and Hata, 2012;Voelkl et al, 2013;Guo et al, 2016). TGF-β-activated transcription factors include SMAD2 and SMAD3.…”

Section: Inhibition Of Transcription Factorsmentioning

confidence: 99%

The Enigmatic Role of Serum & Glucocorticoid Inducible Kinase 1 in the Endometrium

Läng

Rajaxavier

Singh

et al. 2020

Front. Cell Dev. Biol.

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The serum-and glucocorticoid-inducible kinase 1 (SGK1) is subject to genetic up-regulation by diverse stimulators including glucocorticoids, mineralocorticoids, dehydration, ischemia, radiation and hyperosmotic shock. To become active, the expressed kinase requires phosphorylation, which is accomplished by PI3K/PDK1 and mTOR dependent signaling. SGK1 enhances the expression/activity of various transport proteins including Na + /K +-ATPase as well as ion-, glucose-, and amino acid-carriers in the plasma membrane. SGK1 can further up-regulate diverse ion channels, such as Na +-, Ca 2+-, K +-and Cl − channels. SGK1 regulates expression/activity of a wide variety of transcription factors (such as FKHRL1/Foxo3a, β-catenin, NFκB and p53). SGK1 thus contributes to the regulation of transport, glycolysis, angiogenesis, cell survival, immune regulation, cell migration, tissue fibrosis and tissue calcification. In this review we summarized the current findings that SGK1 plays a crucial function in the regulation of endometrial function. Specifically, it plays a dual role in the regulation of endometrial receptivity necessary for implantation and, subsequently in pregnancy maintenance. Furthermore, fetal programming of blood pressure regulation requires maternal SGK1. Underlying mechanisms are, however, still ill-defined and there is a substantial need for additional information to fully understand the role of SGK1 in the orchestration of embryo implantation, embryo survival and fetal programming.

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Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by TGF-β1

Cited by 17 publications

References 30 publications

Effects of the Calcium-Activated Chloride Channel Inhibitors T16Ainh-A01 and CaCCinh-A01 on Cardiac Fibroblast Function

Effects of the Calcium-Activated Chloride Channel Inhibitors T16Ainh-A01 and CaCCinh-A01 on Cardiac Fibroblast Function

Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts

The Enigmatic Role of Serum & Glucocorticoid Inducible Kinase 1 in the Endometrium

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