Biochemical and histological impact of direct renin inhibition by aliskiren on myofibroblasts activation and differentiation in bleomycin induced pulmonary fibrosis in adult mice

Asker, Samar A.; Mazroa, Shireen A.; Boshra, Vivian; Hassan, Ahmed M.

doi:10.1016/j.tice.2015.05.001

Cited by 8 publications

(6 citation statements)

References 54 publications

(60 reference statements)

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“…Currently, treatment options for idiopathic pulmonary fibrosis are limited, leaving most patients with a poor prognosis -the median survival rate is 2-5 years. Several studies in animals (i.e., mice and rats) with bleomycin-induced lung injury showed that Ang II contributes to pulmonary fibrosis, whereas treatment with renin inhibitors, ACE inhibitors, and ARBs attenuates disease progression [73][74][75][76][77]. In this same animal model, intratracheal administration of AGT ASO was found to decrease pulmonary AGT concentrations and lung fibrosis [78], but no comparison was made to conventional RAAS inhibitors.…”

Section: Angiotensinogen Rna-based Therapy In Other Diseasesmentioning

confidence: 89%

Targeting angiotensinogen with RNA-based therapeutics

Ren

Colafella

Bovée

et al. 2020

Current Opinion in Nephrology and Hypertension

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Purpose of review To summarize all available data on targeting angiotensinogen with RNA-based therapeutics as a new tool to combat cardiovascular diseases. Recent findings Liver-targeted, stable antisense oligonucleotides and small interfering RNA targeting angiotensinogen are now available, and may allow treatment with at most a few injections per year, thereby improving adherence. Promising results have been obtained in hypertensive animal models, as well as in rodent models of atherosclerosis, polycystic kidney disease and pulmonary fibrosis. The next step will be to evaluate the optimal degree of suppression, synergy with existing renin-angiotensin-aldosterone system blockers, and to determine harmful effects of suppressing angiotensinogen in the context of common comorbidities, such as heart failure and chronic kidney disease.

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Section: Angiotensinogen Rna-based Therapy In Other Diseasesmentioning

confidence: 89%

Targeting angiotensinogen with RNA-based therapeutics

Ren

Colafella

Bovée

et al. 2020

Current Opinion in Nephrology and Hypertension

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“…EMT, which is a hallmark of IPF, was induced by TGF-β via the RAS and MAPK pathway (51). Additionally, Renin inhibition by aliskiren has been reported to attenuate lung fibrosis, which decreases TGF-β and prevents myofibroblasts activation and differentiation in the BLMinduced IPF model (52). Overall, D-4F ameliorated BLMinduced lung injury and decreased the levels of TGF-β via the Ras/MAPK pathway.…”

Section: Discussionmentioning

confidence: 95%

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis

Xia¹,

Cheng²,

Hu³

et al. 2021

Ann Transl Med

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Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that leads to respiratory failure, and for which there is no effective treatment. Apolipoprotein A-1 (ApoA-1) has been reported to ameliorate the bleomycin (BLM)-induced IPF model. Methods:To examine the function of D-4F, an ApoA-1 mimetic polypeptide, in IPF, we used an in-vivo BLM-induced model. We assigned mice into the following 3 groups: the Blank Group (BLK Group), the Bleomycin Treatment Group (Model Group), and the D-4F Interference Group (Inter Group). The BLM-induced fibrosis was examined by hematoxylin and eosin, Masson's trichrome (M-T) staining and immunohistochemical staining. An untargeted lipidomic and transcriptomic analysis were used to examine the function of D-4F.Results: There were 35 differentially altered lipids (DALs) in the BLK, Model and Inter Groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that glycerophospholipid metabolism was the most highly enriched of the 35 DALs. There were 99 differentially expressed genes (DEGs) in the BLK, Model and Inter Groups. The enriched KEGG pathway analysis showed that the mitogen-activated protein kinase (MAPK) pathway was 1 of the top 10 pathways. The results of the untargeted lipidomic and transcriptomic analysis showed that phospholipase A2 group 4c (Pla2g4c) was a crucial gene in both the MAPK pathway and glycerophospholipid metabolism. Pla2g4c was increased in the Model Group but decreased in the Inter Group.Conclusions: It may be that D-4F prevented the BLM-induced pulmonary fibrosis model by inhibiting the expression of pla2g4c. Our findings suggest that D-4F may be a potential treatment of IPF.

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“…TGF‐β1 plays fundamental roles in the following processes: modulation of cell growth, maturation and differentiation, the formation of ECM, homeostasis, plasticity of endothelial cells, immune regulation, apoptosis, angiogenesis and cancer progression (Heldin, Landström, & Moustakas, ; Ikushima & Miyazono, ; Moses & Barcellos‐Hoff, ; Parvani, Taylor, & Schiemann, ; Van Meeteren & Ten Dijke, ). Its reduction in cardiac, renal, hepatic, lung and peritoneal tissues and in diabetic animals treated with the drug is a beneficial effect (Aihara et al, ; Asker et al, ; Bae et al, ; Baracho et al, ; Choi et al, ; Elrashidy, Asker, & Mohamed, ; Gross et al, ; Kavvadas et al, ; Ke et al, ; Kishina et al, ; Lee, Chan, Hsieh, Huang, & Lin, ; Lizakowski et al, ; Sakuraya et al, ; Sun et al, ; Wang et al, ; Weng et al, ; Wu et al, ; Yamada et al, ; Zhao et al, ; Zhou, Liu, Cheung, & Huang, ).…”

Section: Discussionmentioning

confidence: 99%

The use of aliskiren as an antifibrotic drug in experimental models: A systematic review

Marin

Bertassoli²,

Carvalho

et al. 2019

Drug Development Research

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Aliskiren is an oral antihypertensive medication that acts by directly inhibiting renin. High levels of circulating renin and prorenin activate the pathological signaling pathway of fibrosis. This drug also reduces oxidative stress. Thus, the aim of this systematic review is to analyze experimental studies that show the actions of aliskiren on fibrosis. PubMed and LILACS databases were consulted using the keywords aliskiren and fibrosis within the period between 2005 and 2017. Fifty‐three articles were analyzed. In the heart, aliskiren attenuated remodeling, hypertrophy, inflammatory cytokines, collagen deposition, and oxidative stress. In the kidneys, there was a reduction in interstitial fibrosis, the infiltration of inflammatory cells, apoptosis, proteinuria, and in the recruitment of macrophages. In diabetic models, an improvement in the albumin/creatinine relationship and in the insulin pathway in skeletal muscles was observed; aliskiren was beneficial to pancreatic function and glucose tolerance. In the liver, aliskiren reduced fibrosis, steatosis, inflammatory cytokines, and collagen deposition. In the lung and peritoneal tissues, there was a reduction in fibrosis. Many studies have reported on the beneficial effects of aliskiren on endothelial function and arterial rigidity. A reduction in fibrosis in different organs is cited by many authors, which complies with the results found in this review. However, studies diverge on the use of the drug in diabetic patients. Aliskiren has antifibrotic potential in several experimental models, interfering with the levels of fibrogenic cytokines and oxidative stress. Therefore, its use in diseases in which fibrosis plays an important pathophysiological role is suggested.

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Biochemical and histological impact of direct renin inhibition by aliskiren on myofibroblasts activation and differentiation in bleomycin induced pulmonary fibrosis in adult mice

Cited by 8 publications

References 54 publications

Targeting angiotensinogen with RNA-based therapeutics

Targeting angiotensinogen with RNA-based therapeutics

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis

The use of aliskiren as an antifibrotic drug in experimental models: A systematic review

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