Background:
Macrophage infiltration around lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). However, how these two types of cells communicate remains obscure. We previously demonstrated that LRG1 was elevated in the process of kidney injury. Here, we demonstrated that macrophage-derived, LRG1-enriched extracellular vesicles (EVs) exacerbated DN.
Methods:
We induced an experimental T2DM mouse model with a HFD diet for four months. Renal primary epithelial cells and macrophage-derived EVs were isolated from T2D mice by differential ultracentrifugation. To investigate whether lipotoxic TEC-derived EV (EV
e
) activate macrophages, mouse bone marrow-derived macrophages (BMDMs) were incubated with EV
e
. To investigate whether activated macrophage-derived EVs (EV
m
) induce lipotoxic TEC apoptosis, EV
m
were cocultured with primary renal tubular epithelial cells. Subsequently, we evaluated the effect of LRG1 in EV
e
by investigating the apoptosis mechanism.
Results:
We demonstrated that incubation of primary TECs of DN or HK-2 mTECs with lysophosphatidyl choline (LPC) increased the release of EV
e
. Interestingly, TEC-derived EV
e
activated an inflammatory phenotype in macrophages and induced the release of macrophage-derived EV
m
. Furthermore, EV
m
could induce apoptosis in TECs injured by LPC. Importantly, we found that leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV
e
activated macrophages via a TGFβR1-dependent process and that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-enriched EV
m
induced apoptosis in injured TECs via a death receptor 5 (DR5)-dependent process.
Conclusion:
Our findings indicated a novel cell communication mechanism between tubular epithelial cells and macrophages in DN, which could be a potential therapeutic target.
This article introduces a wideband composite antenna with end‐fire radiation. The structure is achieved by uniting a center‐fed microstrip shorted patch and a parasitical monopole. The monopole is vertical to the substrate and work as an electric current source. Because the loaded monopole breaks the symmetry of the center‐fed microstrip antenna, the original patch antenna can work as in‐phase equivalent magnetic current sources radiation. Then complementary sources are generated by orthometric magnetic current source and electric current source. The typical unidirectional radiation capacity has a good endfire beam. The loaded monopole adds a resonant mode to the original microstrip antenna, which makes the composite microstrip‐monopole antenna to exhibit an enhanced bandwidth of 26.9% and an average gain of 7.5 dBi. The complementary sources radiation mechanism can generate special unidirectional radiation patterns in a compact space, so this antenna type is an excellent candidate for array applications. The prototype's planar size is only 0.36λ0 × 0.39λ0 (λ0 is the free space wavelength in center frequency). The eight elements phased array with the proposed antenna show perfect simulated scanning performance.
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