Biology subjects

Wu, C. L.

Publications and source records attributed to Wu, C. L..

3 recordsLinked to original sources

bioRxiv2023

Depletion of tropomyosin 1.6 promotes matrix-degrading phenotype in TGF-β1-induced myofibroblast

Fibroblasts can be transformed into myofibroblasts under pro-fibrotic conditions, which is characterized by increased contractility and reduced matrix degradation. The relationship between contractile activity and matrix degradation is not fully understood. We found that TGF-{beta}1-induced myofibroblast activation occurs on a culture dish, favoring stress fiber formation and inhibiting podosome structures due to high matrix stiffness. To mimic physiological conditions, we cultured fibroblasts on collagen gel. Blocking actomyosin signaling significantly reduced TGF-{beta}1-induced myofibroblast activation. Tpm1.6, an actomyosin-associated contractile unit, was specifically upregulated by TGF-{beta}1 on soft collagen substrates. Depletion of Tpm1.6 attenuated TGF-{beta}1-induced increase of -SMA, N-cadherin, and {beta}1-integrin, indicating its crucial role in early myofibroblast activation during fibrosis progression. Tpm1.6 depletion reduced TGF-{beta}1-induced cell contractility and enhanced collagen degradation. Notably, in Tpm1.6-depleted fibroblasts, TGF-{beta}1 triggered formation of distinct -SMA dot structures enriched with MMP9, promoting collagen degradation. Our study highlights the pivotal role of Tpm1.6 in TGF-{beta}1-induced myofibroblast activation and collagen degradation. Depletion of Tpm1.6 triggers robust collagen degradation through distinct -SMA dots, presenting a potential therapeutic approach for chronic kidney disease.

cell biology↗

bioRxiv2021

MIAAIM: Multi-omics image integration and tissue state mapping using topological data analysis and cobordism learning

High-parameter tissue imaging enables detailed molecular analysis of single cells in their spatial environment. However, the comprehensive characterization and mapping of tissue states through multimodal imaging across different physiological and pathological conditions requires data integration across multiple imaging systems. Here, we introduce MIAAIM (Multi-omics Image Alignment and Analysis by Information Manifolds) a modular, reproducible computational framework for aligning data across bioimaging technologies, modeling continuities in tissue states, and translating multimodal measures across tissue types. We demonstrate MIAAIMs workflows across diverse imaging platforms, including histological stains, imaging mass cytometry, and mass spectrometry imaging, to link cellular phenotypic states with molecular microenvironments in clinical biopsies from multiple tissue types with high cellular complexity. MIAAIM provides a robust foundation for the development of computational methods to integrate multimodal, high-parameter tissue imaging data and enable downstream computational and statistical interrogation of tissue states.

systems biology↗

bioRxiv2019

Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66-independent targeting of NogoA

NogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction with its receptors, Nogo66/NgR. Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways. We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM. Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway. Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1-G93A. Thus, Pgk1 secreted from muscle is detrimental to motoneuron synapse growth and maintenance.

developmental biology↗