CD2-associated protein/phosphoinositide 3-kinase signaling has a preventive role in angiotensin II-induced podocyte apoptosis
| Autor: | Tae-Sun Ha, Seo-Yun Min, Hye-Young Park, Su-Bin Seong |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Morpholines 030232 urology & nephrology Apoptosis Biochemistry Receptor Angiotensin Type 1 Podocyte Nephrin Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences Paracrine signalling chemistry.chemical_compound 0302 clinical medicine medicine Animals LY294002 Autocrine signalling Protein kinase B Adaptor Proteins Signal Transducing Dose-Response Relationship Drug biology Podocytes Angiotensin II Cell Biology Cytoskeletal Proteins Protein Transport 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation chemistry Chromones Gene Knockdown Techniques Slit diaphragm Cancer research biology.protein Signal Transduction |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 79:370-381 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2016.08.042 |
| Popis: | Angiotensin II (Ang II) works as a paracrine or autocrine cytokine agent to regulate renal functions and promotes podocytes dysfunction directly or indirectly, causing proteinuria. The glomerular slit diaphragm (SD) serves as a size-selective barrier and is linked to the actin-based cytoskeleton by adaptor proteins, including CD2-associated protein (CD2AP). Therefore, damages to CD2AP affect not only the function of the SD, but also directly disrupt the podocyte cytoskeleton, leading to proteinuria. In addition, CD2AP can facilitate the nephrin-induced phosphoinositide 3-kinase (PI3-K)/Akt signaling, which protects podocytes from apoptosis. Here we found that CD2AP staining was located diffusely but predominantly in the peripheral cytoplasm and CD2AP co-localized with nephrin in mouse podocytes; however, Ang II decreased CD2AP staining diffusely and induced a separation from concentrated nephrin. Ang II notably reduced CD2AP expression in time- and concentration-dependent manners, and this was significantly recovered by losartan. Ang II induced podocyte apoptosis in time- and concentration-dependent manners in TUNEL and FACS assays. LY294002, a PI3-K inhibitor, further reduced CD2AP expression and increased podocyte apoptosis, which was augmented by siRNA for CD2AP. Thus, Ang II induces the relocalization and reduction of CD2AP via AT1R, which would cause podocyte apoptosis by the suppression of CD2AP/PI3-K signaling. |
| Databáze: | OpenAIRE |
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