ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2020
Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI-1/Serpine1) Null Mice.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Transcriptomic and functional comparison of adipose-and bone marrow-derived mesenchymal stem cells for tendon regeneration.Stem cell research & therapy · 2026Article
- A spatiotemporal atlas of senescence-associated secretory phenotype in fracture healing: stage-dependent mechanisms and therapeutic windows.Inflammation and regeneration · 2026Review
- Challenge of Corneal Ulcer Healing: A Novel Conceptual Framework, the "Triad" of Corneal Ulcer Healing/Corneal Neovascularization/Intraocular Pressure, and Avascular Tendon Healing, for Evaluation of Corneal Ulcer Therapy, Therapy of Neovascularization, Glaucoma Therapy, and Pentadecapeptide BPC 157 Efficacy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Hypoxia and Foxn1 alter the proteomic signature of dermal fibroblasts to redirect scarless wound healing to scar-forming skin wound healing in Foxn1BMC biology · 2024Article
- Study of the Synergistic Immunomodulatory and Antifibrotic Effects of Dual-Loaded Budesonide and Serpine1 siRNA Lipid-Polymer Nanoparticles Targeting Macrophage Dysregulation in Tendinopathy.ACS applied materials & interfaces · 2024Article
- PAI-1 mediates TGF-β1-induced myofibroblast activation in tenocytes via mTOR signaling.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Review
- Establishing in vivo and ex vivo chick embryo models to investigate fetal tendon healing.Scientific reports · 2023Article
- Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.Biochemical and biophysical research communications · 2022Article
- Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse.Scientific reports · 2022Article
- Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection: a theoretical perspective.Pharmacological reports : PR · 2021Review
- Atorvastatin Inhibits Endothelial PAI-1-Mediated Monocyte Migration and Alleviates Radiation-Induced Enteropathy.International journal of molecular sciences · 2021Article
- NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival.Science signaling · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Injuries to flexor tendons can be complicated by fibrotic adhesions, which severely impair the function of the hand. Plasminogen activator inhibitor 1 (PAI-1/SERPINE1), a master suppressor of fibrinolysis and protease activity, is associated with adhesions. Here, we used next-generation RNA sequencing (RNA-Seq) to assess genome-wide differences in messenger RNA expression due to PAI-1 deficiency after zone II flexor tendon injury. We used the ingenuity pathway analysis to characterize molecular pathways and biological drivers associated with differentially expressed genes (DEG). Analysis of hundreds of overlapping and DEG in PAI-1 knockout (KO) and wild-type mice (C57Bl/6J) during tendon healing revealed common and distinct biological processes. Pathway analysis identified cell proliferation, survival, and senescence, as well as chronic inflammation as potential drivers of fibrotic healing and adhesions in injured tendons. Importantly, we identified the activation of PTEN signaling and the inhibition of FOXO1-associated biological processes as unique transcriptional signatures of the healing tendon in the PAI-1/Serpine1 KO mice. Further, transcriptomic differences due to the genetic deletion of PAI-1 were mechanistically linked to PI3K/Akt/mTOR, PKC, and MAPK signaling cascades. These transcriptional observations provide novel insights into the biological roles of PAI-1 in tendon healing and could identify therapeutic targets to achieve scar-free regenerative healing of tendons. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:43-58, 2020.
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