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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Microglial CD74 Expression Is Regulated by TGFβ Signaling
Jannik Jahn1, Antonia Bollensdorf1, Christopher Kalischer1
1Institute of Anatomy, University Medicine Rostock, University of Rostock, 18051 Rostock, Germany.
Abstract:
Microglia play important roles during physiological and pathological situations in the CNS. Several reports have described the expression of Cd74 in disease-associated and aged microglia. Here, we demonstrated that TGFβ1 controled the expression of Cd74 in microglia in vitro and in vivo. Using BV2 cells, primary microglia cultures as well as Cx3cr1 in combination with qPCR, flow cytometry, and immunohistochemistry, we were able to provide evidence that TGFβ1 inhibited LPS-induced upregulation of Cd74 in microglia. Interestingly, TGFβ1 alone was able to mediate downregulation of CD74 in vitro. Moreover, silencing of TGFβ signaling in vivo resulted in marked upregulation of CD74, further underlining the importance of microglial TGFβ signaling during regulation of microglia activation. Taken together, our data indicated that CD74 is a marker for activated microglia and further demonstrated that microglial TGFβ signaling is important for regulation of Cd74 expression during microglia activation.
Insights
Transforming growth factor beta 1 (TGFβ1) regulates CD74 expression in microglia, a key cell in the central nervous system. This finding highlights TGFβ1
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are crucial immune cells in the central nervous system (CNS), involved in both normal function and disease states.
- Previous studies indicated CD74 (also known as invariant chain) expression in aged and disease-associated microglia.
Purpose of the Study:
- To investigate the role of transforming growth factor beta 1 (TGFβ1) in regulating CD74 expression in microglia.
- To elucidate the functional significance of microglial TGFβ1 signaling in the context of microglial activation.
Main Methods:
- Utilized BV2 cell lines and primary microglia cultures for in vitro experiments.
- Employed Cx3cr1-reporter mice for in vivo studies.
- Applied quantitative real-time PCR (qPCR), flow cytometry, and immunohistochemistry for molecular and cellular analyses.
Main Results:
- TGFβ1 significantly inhibited the lipopolysaccharide (LPS)-induced upregulation of CD74 in microglia, both in vitro and in vivo.
- TGFβ1 alone mediated the downregulation of CD74 expression in microglia cultures.
- Inhibition of TGFβ signaling in vivo led to a notable increase in CD74 expression, confirming TGFβ1's regulatory role.
Conclusions:
- CD74 serves as a reliable marker for activated microglia.
- Microglial TGFβ signaling is a critical regulator of CD74 expression during microglial activation processes.
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