Rapid LC-MS/MS Evaluation of Collagen and Elastin Crosslinks in Human and Mouse Lung Tissue with a Novel Bioanalytical Surrogate Matrix Approach DOI Open Access
S. Lloyd,

Elizabeth J. Sande,

Kenneth J. Ruterbories

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13026 - 13026

Published: Dec. 4, 2024

Alterations to post-translational crosslinking modifications in the extracellular matrix (ECM) are known drive pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Thus, methodology for measuring dynamics is valuable understanding disease progression. The existing analysis sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods typically labor-intensive time-consuming which limits throughput. We, therefore, developed a rapid approach minimizing specialized equipment hands-on time. LC-MS/MS time was reduced two minutes per sample. We then improved analytical integrity method by developing novel surrogate dihydroxylysinonorleucine (DHLNL) crosslink. By modifying preparation, we prepared tissue-based with undetectable levels endogenous DHLNL, providing strategy quantifying this crosslink more relevant standard matrix. applied evaluating lung fibrosis. showed an increase DHLNL human IPF relative healthy donors, as well mouse model. Finally, demonstrated that could be mitigated anti-fibrotic compound, suggesting assay has potential pharmaceutical compound efficacy.

Language: Английский

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis DOI Open Access
S. Lloyd, Yupeng He

Published: Feb. 13, 2024

The extracellular matrix (ECM) provides structural support for tissues and regulatory signals resident cells. ECM requires a careful balance between protein accumulation degradation homeostasis. Disruption of this can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications proteins collagens alter structure function. Dysregulation enzymes well changes composition are prevalent fibrosis. Because crucial roles that pathways play disease, govern events being explored therapeutic targets Here we review in-depth molecular mechanisms underlying crosslinking, how contributes fibrosis, strategies target restore normal tissue

Language: Английский

Citations

4
The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen DOI Open Access
Francisco Revert‐Ros, Ignacio Ventura, Jesús A. Prieto-Ruiz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6523 - 6523

Published: June 13, 2024

Collagen, a versatile family of proteins with 28 members and 44 genes, is pivotal in maintaining tissue integrity function. It plays crucial role physiological processes like wound healing, hemostasis, pathological conditions such as fibrosis cancer. Collagen target these processes. Direct methods for collagen modulation include enzymatic breakdown molecular binding approaches. For instance, Clostridium histolyticum collagenase effective treating localized fibrosis. Polypeptides collagen-binding domains offer promising avenues tumor-specific immunotherapy drug delivery. Indirect targeting involves regulating cellular essential its synthesis maturation, translation regulation microRNA activity. Enzymes involved modification, prolyl-hydroxylases or lysyl-oxidases, are also indirect therapeutic targets. From another perspective, natural source drugs. Enzymatic degradation generates bioactive fragments known matrikines matricryptins, which exhibit diverse pharmacological activities. Overall, collagen-derived peptides present significant potential beyond repair, offering various strategies fibrosis, cancer, genetic disorders. Continued research into specific the application derivatives may lead to development novel treatments range conditions.

Language: Английский

Citations

4
Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming DOI Creative Commons
Ilya Klabukov, Alexander E. Kabakov, A. O. Yakimova

et al.

Current Oncology, Journal Year: 2025, Volume and Issue: 32(2), P. 79 - 79

Published: Jan. 30, 2025

Chimeric antigen receptor (CAR)-T cell therapy yields good results in the treatment of various hematologic malignancies. However, efficacy CAR-T against solid tumors has proven to be limited, primarily because tumor-associated extracellular matrix (ECM) creates an intractable barrier for cytotoxic cells that are supposed kill cancer cells. This review unravels multifaceted role ECM impeding infiltration, survival, and functions within tumors. We analyze situations when intratumoral limits by being a purely physical complicates lymphocyte penetration/migration also acts as immunosuppressive factor impairs antitumor activities In addition, we highlight promising approaches such engineering with improved capabilities penetrate migrate into/through ECM, combination therapies aimed at attenuating high density potential others enable overcoming ECM-related obstacles. A detailed overview data relevant studies not only helps better understand interactions between but outlines ways more effectively use

Language: Английский

Citations

0
Rapid LC-MS/MS Evaluation of Collagen and Elastin Crosslinks in Human and Mouse Lung Tissue with a Novel Bioanalytical Surrogate Matrix Approach DOI Open Access
S. Lloyd,

Elizabeth J. Sande,

Kenneth J. Ruterbories

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13026 - 13026

Published: Dec. 4, 2024

Alterations to post-translational crosslinking modifications in the extracellular matrix (ECM) are known drive pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Thus, methodology for measuring dynamics is valuable understanding disease progression. The existing analysis sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods typically labor-intensive time-consuming which limits throughput. We, therefore, developed a rapid approach minimizing specialized equipment hands-on time. LC-MS/MS time was reduced two minutes per sample. We then improved analytical integrity method by developing novel surrogate dihydroxylysinonorleucine (DHLNL) crosslink. By modifying preparation, we prepared tissue-based with undetectable levels endogenous DHLNL, providing strategy quantifying this crosslink more relevant standard matrix. applied evaluating lung fibrosis. showed an increase DHLNL human IPF relative healthy donors, as well mouse model. Finally, demonstrated that could be mitigated anti-fibrotic compound, suggesting assay has potential pharmaceutical compound efficacy.

Language: Английский

Citations

0