Rank Order Reduction Based Fast Pattern Matching Algorithm

Jaiswal, Himanshu; Dev, Deep Suman; Kisku, Dakshina Ranjan

doi:10.1007/978-981-10-6430-2_24

Cited by 1 publication

(2 citation statements)

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“…Because some reports have shown that the Smad1/5/(8)9 pathway plays a crucial antifibrotic role in renal and liver 39 – 41 , further analyses were performed to assess TGF-β 1 /Smad1/5/9 pathway activity in the HBF populations from asthmatic and non-asthmatic donors. RT-qPCR studies showed that the Smad1 and Smad5 levels were fivefold and tenfold higher, respectively, in HBFs derived from AS donors (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Smad1/5/9 pathway activation has been shown previously to have potent antifibrotic effects in liver fibrosis 41 , renal fibrosis 39,60 , pulmonary fibrosis [61][62][63] and myocardial fibrosis 64 in animals and humans. We reported that TGF-β/Smad1/5/9 pathway activity is increased in HBFs from non-asthmatic donors compared to HBFs obtained from patients with asthma.…”

Section: Discussionmentioning

confidence: 98%

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Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment

Wnuk

Paw

Ryczek

et al. 2020

Sci Rep

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Airway remodelling with subepithelial fibrosis, which abolishes the physiological functions of the bronchial wall, is a major issue in bronchial asthma. Human bronchial fibroblasts (HBFs) derived from patients diagnosed with asthma display in vitro predestination towards TGF-β1-induced fibroblast-to-myofibroblast transition (FMT), a key event in subepithelial fibrosis. As commonly used anti-asthmatic drugs do not reverse the structural changes of the airways, and the molecular mechanism of enhanced asthma-related TGF-β1-induced FMT is poorly understood, we investigated the balance between the profibrotic TGF-β/Smad2/3 and the antifibrotic TGF-β/Smad1/5/9 signalling pathways and its role in the myofibroblast formation of HBF populations derived from asthmatic and non-asthmatic donors. Our findings showed for the first time that TGF-β-induced activation of the profibrotic Smad2/3 signalling pathway was enhanced, but the activation of the antifibrotic Smad1/5/(8)9 pathway by TGF-β1 was significantly diminished in fibroblasts from asthmatic donors compared to those from their healthy counterparts. The impairment of the antifibrotic TGF-β/Smad1/5/(8)9 pathway in HBFs derived from asthmatic donors was correlated with enhanced FMT. Furthermore, we showed that Smad1 silencing in HBFs from non-asthmatic donors increased the FMT potential in these cells. Additionally, we demonstrated that activation of antifibrotic Smad signalling via BMP7 or isoliquiritigenin [a small-molecule activator of the TGF-β/Smad1/5/(8)9 pathway] administration prevents FMT in HBFs from asthmatic donors through downregulation of profibrotic genes, e.g., α-SMA and fibronectin. Our data suggest that influencing the balance between the antifibrotic and profibrotic TGF-β/Smad signalling pathways using BMP7-mimetic compounds presents an unprecedented opportunity to inhibit subepithelial fibrosis during airway remodelling in asthma.

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Section: Resultsmentioning

confidence: 99%