Journal
EXPERIMENTAL CELL RESEARCH
Volume 383, Issue 1, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.111504
Keywords
Myofibroblast; p75(NTR); NGF; MRTF-A; Differentiation
Categories
Funding
- National Natural Science Foundation of China [81571911, 81772092]
- Science and Technology Development Program of Shandong Province [2016GSF201080]
Ask authors/readers for more resources
Myofibroblasts are characterized by de novo expression of a-smooth muscle actin (alpha-SMA) and play a key role in tissue repair and remodeling. In addition to TGF-beta 1, recent studies have shown that nerve growth factor (NGF) has effects on myofibroblast differentiation and collagen synthesis. However, the regulatory mechanism remains poorly defined. NGF effects are mediated by the specific expression of the NGF neurotrophic tropomyosin-receptor kinase A (TrkA) and p75 neurotrophin receptor (p75(NTR)). Using NIH/3T3 fibroblast cell lines, we examined the induction of myofibroblast differentiation stimulated by NGF. Our findings showed that p75(NTR) was in keeping with the expression of alpha-SMA. Herein, we investigated the role of p75(NTR) in NGF-induced myofibroblast differentiation and collagen synthesis in these cells using lentivirus transfection to overexpress and knock down. Our results showed that p75 NTR was preferentially expressed and was sufficient to induce actin cytoskeleton remodeling, which was required for NGF-induced alpha-SMA expression. Furthermore, NGF induced nuclear translocation of MRTF-A, an effect that was regulated by p75(NTR), and required for alpha-SMA and collagen-I expression in myofibroblasts. Using a novel MRTF-A pathway inhibitor, CCG-203971, we further demonstrated the requirement of MRTF-A nuclear localization and activity in NGF-induced alpha-SMA expression. In conclusion, we conclude that p75(NTR) regulates NGF-induced myofibroblast differentiation and collagen synthesis through MRTF-A. Regulation of NGF-p75(NTR) interactions represents a promising therapy for fibrotic disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available