@article{23551,
  keywords = {Adult, Cell Differentiation, Cells, Cultured, Female, Fibrosis, Humans, Inflammation Mediators, leprosy, Male, Middle Aged, Mycobacterium leprae, Neurons, Schwann Cells, Transforming Growth Factor beta1, Young Adult},
  author = {Petito RB and Amadeu TP and Pascarelli B and Jardim M and Vital R and Antunes S and Sarno E},
  title = {Transforming growth factor-β1 may be a key mediator of the fibrogenic properties of neural cells in leprosy.},
  abstract = {<p>Fibrosis is the main cause of irreversible nerve damage in leprosy. Phenotypic changes in Mycobacterium leprae (ML)-infected Schwann cells (SCs) have been suggested to mediate this process. We found that SC line cultures stimulated with ML upregulated transforming growth factor-β1 (TGF-β1), and that TGF-β1 or ML induced increased numbers of α-smooth muscle actin (α-SMA)-positive cells with characteristic stress fibers. Mycobacterium leprae and TGF-β1 also induced increased type I collagen and fibronectin mRNA and secretion and augmented mRNA levels of SOX9 and ZEB1, which are involved in the epithelial-mesenchymal transition. These effects could be inhibited by the TGF-β1 type I receptor (ALK5) inhibitor, SB-431542. In nerve biopsies from leprosy-infected patients with varying grades of fibrosis (n = 11), type I and III collagen and fibronectin were found in the endoneurium and perineurium, α-SMA-positive cells filled the fibrotic perineurium but not the endoneurium, and CD34-positive fibroblasts predominated in the endoneurium. Results of transcriptional studies of 3 leprosy nerves and 5 controls were consistent with these data, but α-SMA and other mRNA levels were not different from those in the control samples. Our findings suggest that TGF-β1 may orchestrate events, including reprogramming of the SC phenotype, leading to transdifferentiation, connective tissue cell expansion, and fibrogenesis in the evolution of leprosy nerve lesions during some evolutionary stages.</p>},
  year = {2013},
  journal = {Journal of neuropathology and experimental neurology},
  volume = {72},
  pages = {351-66},
  month = {2013 Apr},
  issn = {1554-6578},
  doi = {10.1097/NEN.0b013e31828bfc60},
  language = {eng},
}