Premium
Phenformin Inhibits Myofibroblast Differentiation in Dupuytren's Contracture Cells Treated with TGF‐β1
Author(s) -
McNamar Rachel Anae,
Vaughan Melville B
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1034.13
Subject(s) - myofibroblast , phenformin , metformin , chemistry , cancer research , transforming growth factor beta , cellular differentiation , transforming growth factor , microbiology and biotechnology , endocrinology , medicine , biology , fibrosis , diabetes mellitus , biochemistry , gene
Metformin and phenformin have been used to help treat type‐2 diabetes. Recently, these two compounds have been found to have antifibrotic effects in tissues that are proliferative and myofibroblast‐rich. Metformin and phenformin could be utilized to help treat Dupuytren's contracture by inhibiting the differentiation of myofibroblasts. Myofibroblasts are characterized by an abundance of alpha smooth muscle actin (αSMA) within stress fibers in the cytoplasm of the cell. Transforming growth factor beta 1 (TGF‐β1) has been used to upregulate the formation of αSMA and used to promote myofibroblast differentiation. Myofibroblast differentiation is thought to be inhibited by metformin and phenformin because they activate the AMP‐activated kinase (AMPK) pathway. This pathway has been found to inhibit TGF‐β1 induced myofibroblast differentiation. This study examined the inhibitory effects of myofibroblast differentiation and proliferation that metformin and phenformin have on Dupuytren's contracture (DC) cells treated with TGF‐β1. To investigate these inhibitory effects, four treatment groups of DC cells were cultured for 48 hours and analyzed. One group acted as a control, while the other three were treated with TGF‐β1. Two of those three groups were also treated with either metformin or phenformin. Proliferation was determined using a click‐EdU culturing and staining procedure; differentiation was determined by visualizing alpha‐smooth muscle actin (αSMA) using immunocytochemistry. Through qualitative analysis of the data collected through fluorescence microscopy, the group treated with phenformin demonstrated suppression of myofibroblast differentiation and had no effect on cell proliferation. The metformin‐treated group showed no obvious effect on the suppression of myofibroblast differentiation and showed a slight increase in proliferating cells. Our future goal is to determine whether a higher dose of metformin will demonstrate similar results to phenformin and other AMP‐K activators. These results will be supplemented using other myofibroblast‐appropriate functional bioassays. Support or Funding Information Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number 8P20GM103447.