A secretome screen in primary human lung fibroblasts identifies FGF9 as a novel regulator of cellular senescence.

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Tác giả: Jenna Bradley, Davide Gianni, Johann Mattsson, Henric Olsson, Patrick O'Shea, Catherine Overed-Sayer, Roxane Paulin, Laura Rosenberg, Catherine Wrench

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : SLAS discovery : advancing life sciences R & D , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 740625

Senescent cells contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a disease with significant unmet need and therefore, there is an interest in discovering new drug targets that regulate this process. We design and perform a phenotypic screen with a secreted protein library in primary human lung fibroblasts to identify modulators of cell senescence. We identify FGF9 as a suppressor of several senescence phenotypes reducing stimulated p21 expression, enlarged morphology, DNA damage and SASP secretion, which is consistent with both DNA-damage and ROS induced senescence. We also show that FGF9 reduces fibroblast activation in both healthy and IPF fibroblasts shown by a reduction in pro-fibrotic markers such as α-smooth muscle actin and COL1A1 mRNA. Our findings identify FGF9 as a suppressor of both senescence and fibrotic features in lung fibroblasts and therefore could be targeted as a new therapeutic strategy for respiratory diseases such as IPF.
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