The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Tissue fibrosis is characterized by uncontrolled deposition and diminished clearance of fibrous connective tissue proteins, ultimately leading to organ scarring. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) have recently emerged as pivotal drivers of mesenchymal cell activation in human fibrosis. Therapeutic strategies inhibiting YAP and TAZ have been hindered by the critical role that these proteins play in regeneration and homeostasis in different cell types. Here, we find that the Gαs-coupled dopamine receptor D1 (DRD1) is preferentially expressed in lung and liver mesenchymal cells relative to other resident cells of these organs. Agonism of DRD1 selectively inhibits YAP/TAZ function in mesenchymal cells and shifts their phenotype from profibrotic to fibrosis resolving, reversing in vitro extracellular matrix stiffening and in vivo tissue fibrosis in mouse models. Aromatic l-amino acid decarboxylase [DOPA decarboxylase (DDC)], the enzyme responsible for the final step in biosynthesis of dopamine, is decreased in the lungs of subjects with idiopathic pulmonary fibrosis, and its expression inversely correlates with disease severity, consistent with an endogenous protective role for dopamine signaling that is lost in pulmonary fibrosis. Together, these findings establish a pharmacologically tractable and cell-selective approach to targeting YAP/TAZ via DRD1 that reverses fibrosis in mice. Via Science Translational Medicine.
Published to PubMed This Week
- Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis.
Clinical Infectious Disease
- Collapsin Response-Mediator Protein 5-Associated Retinitis, Vitreitis, and Optic Disc Edema.
- Use of Troponins in Clinical Practice: Evidence in Favour of Use of Troponins in Clinical Practice.
- Pathology of Breast Cancer in the Last Half Century.
- "Hey! Whatever Happened to Hemangiopericytoma and Fibrosarcoma?" An Update on Selected Conceptual Advances in Soft Tissue Pathology Which Have Occurred over the Past 50 Years.
- What Do Former Residents Say about Their Nondesignated Preliminary Year? A Survey of Prelims' Experiences in a General Surgery Residency Program.
Journal of Surgery Education
- Estimating Short- and Long-term Reference Change Values and Index of Individuality for Tests of Platelet Function.
- Myeloid Sarcoma with CBFB-MYH11 Fusion (inv(16) or t(16;16)) Prevails in the Abdomen.
American Journal of Clinical Pathology
- Usefulness of CT Texture Analysis in Differentiating Benign and Malignant Renal Tumors.
- A Report of a Caliber-Persistent Labial Artery Accompanied by Uncharacteristic Symptomology.
Journal of Stomatology, Oral, and Maxillofacial Surgery