What question did this study set out to answer?

The aim is to evaluate how the extracellular matrix (ECM) influenced by MRC2 deficiency affects lung fibroblast behavior.

May 20, 2026

C71-12 Mrc2-Deficient Cell-Derived Matrix Modulates Lung Fibroblast Profibrotic-like Characteristics

Key Points

The aim is to evaluate how the extracellular matrix (ECM) influenced by MRC2 deficiency affects lung fibroblast behavior.
Primary lung fibroblasts cultured from wild-type and MRC2-null mice for 14 days.
Cell-derived matrices were decellularized and reseeded with WT or MRC2-null cells.
RNA was extracted for quantitative real-time PCR (qPCR) analysis post-reseeding.
WT fibroblasts on MRC2-null ECM showed increased Yap, Taz, and Tgfb1 expression compared to those on WT ECM.
MRC2-null fibroblasts displayed similar results when on MRC2-null matrix, indicating a matrix-driven phenotype.

Abstract

Abstract Rationale Mannose Type C receptor (MRC2) is a fibroblast-enriched endocytic receptor in the lung that is critical for collagen turnover. Dysregulation of MRC2-mediated collagen uptake has been implicated in the development of lung fibrosis. In previous studies, we demonstrated that MRC2-null mice exhibit increased lung stiffness at baseline, despite no detectable changes in total collagen content as measured by hydroxyproline. Furthermore, lung fibroblasts from MRC2-null mice show enhanced proliferation. Building on these findings, we investigated whether the extracellular matrix (ECM) associated with MRC2 deficiency influences fibroblast phenotype by assessing the expression of Yap/Taz—transcriptional effectors of the Hippo pathway—and TGF-β1, all of which are well-established key regulators of matrix remodeling and fibrosis. Methods Primary mouse lung fibroblasts were harvested from age- and sex-matched wild-type (WT) and MRC2-null mice. Fibroblasts were cultured in 24-well plates for 14 days with ascorbic acid to allow maximal matrix accumulation. The resulting cell-derived matrices were subsequently decellularized, then reseeded with either WT or MRC2-null cells. The cells were then collected 24 hours post-reseeding and RNA was extracted for quantitative real-time PCR (qPCR) analysis. Results qPCR analysis revealed that WT fibroblasts reseeded onto ECM derived from MRC2-null cells exhibited significantly increased expression of Yap, Taz and Tgfb1 compared to those reseeded onto WT ECM. Further, MRC2-null fibroblasts show the same response to MRC2-null matrix suggesting that this fibroblast phenotype is dominated by the matrix and is likely cell-extrinsic. Conclusions MRC2-null fibroblasts produce a matrix that promotes a profibrotic-like phenotype, underscoring the importance of the ECM in shaping fibroblast activation and responses. Ongoing and future studies will assess the effect of the MRC2-null ECM on other aspects of fibroblast biology, such as morphology and proliferation, as well as investigate the key differences in MRC2-null ECM that are responsible for modulating fibroblast phenotype. This abstract is funded by: Department of Defense

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