ArticleMolecular & cellular proteomics : MCP2019
Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts.
Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Impaired collagen deposition in the absence of ERp44.iScience · 2026Article
- Exercise-induced modulation of the unfolded protein response: a therapeutic avenue for muscle wasting disorders.Journal of physiology and biochemistry · 2026Review
- Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress.Antioxidants (Basel, Switzerland) · 2025Review
- New imaging tools reveal live cellular collagen secretion, fibril dynamics and network organisation.Scientific reports · 2025Article
- The Potential Application of Nanocarriers in Delivering Topical Antioxidants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Elucidating Anti-aging and Antioxidant Activity ofCombinatorial chemistry & high throughput screening · 2025Article
- Molecular Characterization and Inhibition of a Novel Stress-Induced Mitochondrial Protecting Role for Misfolded TrkAIII in Human SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2024Article
- Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Skin Aging of Nude Mice Through Autophagy-Mediated Anti-Senescent Mechanism.Stem cell reviews and reports · 2022Article
- Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy.Oxidative medicine and cellular longevity · 2020Review
- Salivary gland proteome analysis of developing adult female Haemaphysalis longicornis ticks: molecular motor and TCA cycle-related proteins play an important role throughout development.Parasites & vectors · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Redox stress is a well-known contributor to aging and diseases in skin. Reductants such as dithiothreitol (DTT) can trigger a stress response by disrupting disulfide bonds. However, the quantitative response of the cellular proteome to reductants has not been explored, particularly in cells such as fibroblasts that produce extracellular matrix proteins. Here, we have used a robust, unbiased, label-free SWATH-MS proteomic approach to quantitate the response of skin fibroblast cells to DTT in the presence or absence of the growth factor PDGF. Of the 4487 proteins identified, only 42 proteins showed a statistically significant change of 2-fold or more with reductive stress. Our proteomics data show that reductive stress results in the loss of a small subset of reductant-sensitive proteins (including the collagens COL1A1/2 and COL3A1, and the myopathy-associated collagens COL6A1/2/3), and the down-regulation of targets downstream of the MAPK pathway. We show that a reducing environment alters signaling through the PDGF-associated MAPK/Akt pathways, inducing chronic dephosphorylation of ERK1/2 at Thr202/Tyr204 and phosphorylation of Akt at Ser473 in a growth factor-independent manner. Our data highlights collagens as sentinel molecules for redox stress downstream of MAPK/Akt, and identifies intervention points to modulate the redox environment to target skin diseases and conditions associated with erroneous matrix deposition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.