Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts

Ana M Diaz-Espinosa; Patrick A Link; Delphine Sicard; Ignasi Jorba; Daniel J Tschumperlin; Andrew J Haak

doi:10.1242/jcs.248278

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Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts

Journal article

Peer reviewed

Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts

Ana M Diaz-Espinosa, Patrick A Link, Delphine Sicard, Ignasi Jorba, Daniel J Tschumperlin and Andrew J Haak

Journal of cell science, Vol.133(23), jcs248278

12/11/2020

DOI: 10.1242/jcs.248278

PMCID: PMC7746663

PMID: 33172983

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https://www.ncbi.nlm.nih.gov/pmc/articles/7746663View

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Abstract

Matrix resorption is essential to the clearance of the extracellular matrix (ECM) after normal wound healing. A disruption in these processes constitutes a main component of fibrotic diseases, characterized by excess deposition and diminished clearance of fibrillar ECM proteins, such as collagen type I. The mechanisms and stimuli regulating ECM resorption in the lung remain poorly understood. Recently, agonism of dopamine receptor D1 (DRD1), which is predominantly expressed on fibroblasts in the lung, has been shown to accelerate tissue repair and clearance of ECM following bleomycin injury in mice. Therefore, we investigated whether DRD1 receptor signaling promotes the degradation of collagen type I by lung fibroblasts. For cultured fibroblasts, we found that DRD1 agonism enhances extracellular cleavage, internalization and lysosomal degradation of collagen I mediated by cathepsin K, which results in reduced stiffness of cell-derived matrices, as measured by atomic force microscopy. agonism of DRD1 similarly enhanced fibrillar collagen degradation by fibroblasts, as assessed by tissue labeling with a collagen-hybridizing peptide. Together, these results implicate DRD1 agonism in fibroblast-mediated collagen clearance, suggesting an important role for this mechanism in fibrosis resolution.This article has an associated First Person interview with the first author of the paper.

Animals

Cathepsin K - genetics

Cells, Cultured

Collagen

Collagen Type I - genetics

Extracellular Matrix

Fibroblasts

Lung

Mice

Receptors, Dopamine D1 - genetics

Details

Title: Subtitle: Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts
Creators: Ana M Diaz-Espinosa - Mayo Clinic
Patrick A Link - Mayo Clinic
Delphine Sicard - Mayo Clinic
Ignasi Jorba - Mayo Clinic
Daniel J Tschumperlin - Mayo Clinic
Andrew J Haak - Mayo Clinic
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.133(23), jcs248278
DOI: 10.1242/jcs.248278
PMID: 33172983
PMCID: PMC7746663
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Grant note: R01 HL092961 / NHLBI NIH HHS R01 HL133320 / NHLBI NIH HHS T32 HL105355 / NHLBI NIH HHS
Language: English
Date published: 12/11/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
Record Identifier: 9984948144002771

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