Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis

Eduardo, Manuel; Ruiz, Vı́ctor; Checa, Marco; Maldonado, Vilma; Meléndez-Zajgla, Jorge; Montaño, Martha; Ordóñez-Razo, Rosa María; Cisneros, José; Alba, Carolina García de; Pardo, Annie; Selman, Moisés

doi:10.1183/09031936.00130310

Cited by 32 publications

(24 citation statements)

References 31 publications

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“…Collagen measurement. Collagen was quantified in cell-conditioned medium using the Sircol collagen assay (Biocolor, Belfast, UK) as described (29).…”

Section: Methodsmentioning

confidence: 99%

Role of Sonic Hedgehog in idiopathic pulmonary fibrosis

Bolaños

Mendoza-Milla

Lira

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

136

135

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Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease of unknown etiology and uncertain pathogenic mechanisms. Recent studies indicate that the pathogenesis of the disease may involve the abnormal expression of certain developmental pathways. Here we evaluated the expression of Sonic Hedgehog (SHH), Patched-1, Smoothened, and transcription factors glioma-associated oncogene homolog (GLI)1 and GLI2 by RT-PCR, as well as their localization in IPF and normal lungs by immunohistochemistry. The effects of SHH on fibroblast proliferation, migration, collagen and fibronectin production, and apoptosis were analyzed by WST-1, Boyden chamber chemotaxis, RT-PCR, Sircol, and annexin V-propidium iodide binding assays, respectively. Our results showed that all the main components of the Sonic signaling pathway were overexpressed in IPF lungs. With the exception of Smoothened, they were also upregulated in IPF fibroblasts. SHH and GLI2 localized to epithelial cells, whereas Patched-1, Smoothened, and GLI1 were observed mainly in fibroblasts and inflammatory cells. No staining was detected in normal lungs. Recombinant SHH increased fibroblast proliferation (P < 0.05), collagen synthesis, (2.5 ± 0.2 vs. 4.5 ± 1.0 μg of collagen/ml; P < 0.05), fibronectin expression (2-3-fold over control), and migration (190.3 ± 12.4% over control, P < 0.05). No effect was observed on α-smooth muscle actin expression. SHH protected lung fibroblasts from TNF-α/IFN-γ/Fas-induced apoptosis (14.5 ± 3.2% vs. 37.3 ± 7.2%, P < 0.0001). This protection was accompanied by modifications in several apoptosis-related proteins, including increased expression of X-linked inhibitor of apoptosis. These findings indicate that the SHH pathway is activated in IPF lungs and that SHH may contribute to IPF pathogenesis by increasing the proliferation, migration, extracellular matrix production, and survival of fibroblasts.

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“…Collagen measurement. Collagen was quantified in cell-conditioned medium using the Sircol collagen assay (Biocolor, Belfast, UK) as described (29).…”

Section: Methodsmentioning

confidence: 99%

Role of Sonic Hedgehog in idiopathic pulmonary fibrosis

Bolaños

Mendoza-Milla

Lira

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

136

135

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“…From another perspective, Molteni et al (83) showed that Ang II receptor inhibitors were helpful in palliating RILI. Additionally, certain researchers suggested renin as a profibrotic mediator independent from the angiotensin system, in the lung and other organs, which may provide another approach to mitigating lung fibrosis (84,85). …”

Section: Treatmentsmentioning

confidence: 99%

Pulmonary toxicity generated from radiotherapeutic treatment of thoracic malignancies

et al. 2017

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Radiation-induced lung injury (RILI) remains a major obstacle for thoracic radiotherapy for the treatment of lung cancer, esophageal cancer and lymphoma. It is the principal dose-limiting complication, and can markedly impair the therapeutic ratio as well as a patient's quality of life. The current review presents the relevant concepts associated with RILI, including the pathogenic mechanisms and the potential treatment strategies, so as to achieve a general understanding of this issue. RILI comprises an acute radiation pneumonitis phase and subsequent late lung fibrosis. The established assessment criteria are clinical manifestations, imaging changes and the necessity for medical assistance. Risk factors are also considered in order to optimize treatment planning. Due to the underlying molecular mechanisms of RILI, the present review also discusses several targeted pharmacological approaches for its treatment, as well as corticosteroid therapy.

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“…Collagen concentration was determined by colorimetric Sircol soluble collagen assay (Biocolor Ltd., Carrickfergus, UK) according to the manufacturer's instructions [22]. Optical density was measured at 555 nm using an ELISA plate reader (Sinergy HT, BioTek).…”

Section: Collagen Assaymentioning

confidence: 99%

Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis

et al. 2012

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Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder characterised by expansion of the myofibroblast population and aberrant lung remodelling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with age but an exaggerated decline has been associated with chronic degenerative diseases.We quantified the plasma levels of DHEA and its sulfated form (DHEA-S) in 137 IPF patients and 58 controls and examined the effects of DHEA on human lung fibroblasts.Plasma DHEA/DHEA-S was significantly decreased in male IPF patients (median (range) DHEA: 4.4 (0.2–29.2)versus6.7 (2.1–15.2) ng·mL−1, p<0.01; DHEA-S: 47 (15.0–211)versus85.2 (37.6–247.0) μg·dL−1, p<0.001), while in females only DHEA-S was significantly decreased (32.6 (15.0–303.0)versus68.3 (16.4–171) μg·dL−1, p<0.001). DHEA caused a decrease in fibroblast proliferation and an approximately two-fold increase in fibroblast apoptosis, probably through the intrinsic pathway with activation of caspase-9. This effect was accompanied by upregulation of several pro-apoptotic proteins (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti-apoptotic proteins, such as cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2. DHEA also caused a significant decrease of transforming growth factor-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited platelet-derived growth factor-induced fibroblast migration.These findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients and indicate that this molecule has multiple antifibrotic properties.

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Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis

Cited by 32 publications

References 31 publications

Role of Sonic Hedgehog in idiopathic pulmonary fibrosis

Role of Sonic Hedgehog in idiopathic pulmonary fibrosis

Pulmonary toxicity generated from radiotherapeutic treatment of thoracic malignancies

Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis

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