Ivermectin as a potential therapeutic for Interstitial Pulmonary Fibrosis

Interstitial pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. The TGF-β1/SMAD3 pathway is a central driver of this process, yet current antifibrotic therapies only slow disease progression and remain costly. Recent studies suggest that ivermectin, a widely available antiparasitic drug, may inhibit SMAD3 phosphorylation in non-pulmonary fibroblasts, raising the question of whether it could attenuate fibrotic signaling in lung fibroblasts. This study investigates whether ivermectin suppresses fibroblast activation in IPF by reducing α-SMA expression, inhibiting SMAD3 phosphorylation, and limiting fibroblast migration. Human lung fibroblasts will be treated with increasing concentrations of ivermectin (0.1–3.0 µM) for 48 hours in the presence of TGF-β1. α-SMA gene expression will be quantified by RT-qPCR, and α-SMA, SMAD3, and pSMAD3 protein levels will be examined by Western blot. Functional effects will be assessed using a scratch wound-healing assay performed in 6-well plates, and actin organization will be visualized with phalloidin staining. Data will be quantified using ImageJ and analyzed with one-way ANOVA. We expect ivermectin to decrease α-SMA expression, reduce SMAD3 phosphorylation, and slow fibroblast migration in a dose-dependent manner. These findings would support the potential repurposing of ivermectin as a low-cost antifibrotic therapy and provide new insight into modulation of the TGF-β1/SMAD3 pathway in pulmonary fibrosis.

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Diya Chordia: Hello, everyone, and thank you for taking the time to come visit my poster. My project focuses on exploring the potential antifibrotic effects of ivermectin and antiparasitic in interstitial pulmonary fibrosis, or IPF. IPF is a progressive and ultimately fatal lung disease characterized by fibroblast activation and

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Diya Chordia: Excessive extracellular matrix deposition.

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Diya Chordia: Although current medications can slow the disease, they cannot reverse fibrosis, and lung transplantation remains the only definitive treatment. Because of this, there is a real need for new, accessible therapeutic options.

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Diya Chordia: A key driver of fibrosis in IPF is the TGF-beta and SMART3 signaling pathway. When activated, this pathway increases the expression of markers such as alpha smooth muscle actin, and promotes structural and functional changes that make fibroblasts more contractile and migratory.

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Diya Chordia: Recent work, including a 2021 paper by Zia et al, suggests that ivermectin can reduce SMART3, activation and decrease

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Diya Chordia: alpha-sma expression in fibroblasts from other tissues. However, its effects on lung fibrosis have not yet been studied. This gap in literature motivated this central research question of my project.

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Diya Chordia: Our hypothesis is that ivermectin will attenuate fibroblast activation in IPF,

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Diya Chordia: by suppressing the SMART3 signaling pathway. Specifically, we predict that ivermectin will decrease alpha-smar expression, reduce SMAR3 phosphorylation or activation, and limit fibroblast migration.

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Diya Chordia: To test our hypothesis, human lung fibroblasts will be treated with increasing concentrations of ivermectin, from 0.1 to 3 micromolar for 48 hours in the presence of, FPS,

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Diya Chordia: to induce activation. Following treatment, SMAR… the alpha-sma gene expression will be measured using RT-QPCR with RNA isolated using the Quergen RNA-Z kit for reliable, high-purity extraction.

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Diya Chordia: Protein expression will be assessed by a Western blot, probing specifically for Alpha SMAR, total SMART3, and phosphorylated SMART3, which is just activated SMART3, using high-specificity antibodies.

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Diya Chordia: To evaluate functional changes, a scratch wound healing assay will be performed in 6 well plates to determine the effect of ivermectin on fibroblast migration.

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Diya Chordia: Falden staining will be used to visualize alternatives in actin organization and stress fiber formation.

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Diya Chordia: All image-based analysis will be quantified using image J.

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Diya Chordia: And data will be statistically evaluated using one-way ANOVA with a significant threshold of, P is less than 0.05.

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Diya Chordia: Although the full results are still being generated, the expected outcomes are that ivermectin will reduce alpha-smar levels.

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Diya Chordia: suppress SMAR3-phosphorylation and slow fibroblast migration in a dose-dependent manner. If these predictions hold true, it would indicate that ivermectin can directly interrupt prohibprotic signal signaling and fibroblast activation.

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Diya Chordia: The broader significance of this work relies in its potential impact on global health.

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Diya Chordia: IPF affects patients worldwide, but access to current drugs is limited by high cost. Because of this, ivermectin is inexpensive, well-studied, and already widely distributed, and identifying antifibrotic activity could make treatment more accessible, especially in low- and middle-income settings.

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Diya Chordia: This study also contributes new insights into how the SMART3 signaling can be modulated in pulmonary fibrosis, providing a foundation for future therapeutic development.

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Diya Chordia: Thank you for listening!