Macrophage migration inhibitory factor regulates integrin-β1 and cyclin D1 expression via ERK pathway in podocytes - 11/02/20
, Jer-Ming Chang c, Yu-Lin Yang d, Eddy-Essen Chang c, Hung-Chun Chen cBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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Graphical abstract |
Highlights |
• | Podocyte injury and proliferation lead to proliferative glomerulonephritis. Iintegrins and cyclin D1 regulate cell proliferation and differentiation. |
• | MIF up-regulated the expression of integrin-β1 and cyclin D1 in podocytes through ERK pathway. MIF also increased podocyte adhesion; however the adhesion was inhibited by anti-integrin-β1 antibody. |
• | This study identifies a novel mechanism for MIF signaling in regulating podocytes adhesion and proliferation. |
Abstract |
Aims |
Macrophage migration inhibitory factor (MIF) is found to increase in proliferative glomerulonephritis. MIF binds to the MIF receptor (CD74) that activates MAP kinase (ERK and p38). Integrins and cyclinD1 regulate cell proliferation, differentiation and adhesion. This study evaluates whether MIF can regulate integrin-β1/cyclin D1 expression and cell adhesion of podocytes.
Main methods |
Expression of integrin-β1 mRNA/protein and cyclin D1 mRNA under stimulation of MIF was evaluated by real-time PCR and Western blotting. MIF receptor (CD74) and MAP kinase under MIF treatment were examined to determine which pathway regulated integrin-β1 and cyclin D1 expression. Cell adhesion was evaluated under MIF treatment and/or anti-integrin-β1 antibody by cell adhesion assay.
Key findings |
Protein levels of integrin-β1 were up-regulated under MIF treatment in a dosage-dependent manner. CD74 protein levels were not changed after MIF treatment. Integrin-β1 and cyclin D1 mRNA levels were up-regulated after MIF 100 ng/ml treatment. ERK inhibitor U0126 reduced MIF-induced the increase in integrin-β1 mRNA and protein expression following MIF stimulation. However, p38 inhibitor SB 203580 did not inhibit MIF-induced increase in integrin-β1 mRNA and protein expression following MIF stimulation. MIF-induced increase in cyclin D1 mRNA level also was inhibited only by U0126 following MIF stimulation. Podocyte adhesion was increased after MIF treatment, but, anti-integrin-β1 antibody decreased MIF-enhanced podocyte adhesion.
Significance |
MIF increases integrin-β1 and cyclin D1 expression through the ERK pathway in podocytes, and the up-regulated expression of integrin-β1 increases podocyte adhesion. These results provide further understanding for the role of MIF in developing proliferative glomerulonephritis.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Macrophage migration inhibitory factor, Integrin β1, Podocytes
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Vol 124
Articolo 109892- aprile 2020 Ritorno al numero
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