Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells
| Autor: | De‑Jun Che, Sha‑Sha Wang, Jing‑Min Zheng, Xiong Tian |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research podocyte Cell chemical and pharmacologic phenomena Arginine Biochemistry Podocyte Cell Line Focal adhesion 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans complement morphological maturation Progenitor cell Benzhydryl Compounds Molecular Biology Complement Activation biology Chemistry Podocytes Regeneration (biology) Transfection Articles Cell cycle Cell biology Receptors Complement 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis biology.protein Complement C3a Molecular Medicine C3a receptor human C3A anaphylatoxin receptor |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | The C3a receptor (C3aR) has been reported to be involved in various physiological and pathological processes, including the regulation of cellular structure development. Expression of C3aR has been reported in podocytes; however, data concerning the role of C3aR in podocyte morphology is scarce. The aim of the present study was to examine the effect of C3aR activation on the architectural development of podocytes. An immortal human podocyte line (HPC) was transfected with a C3a expression lentivirus vector or recombinant C3a. SB290157 was used to block the activation of C3aR. The expression of C3a in HPC cells was analyzed by reverse transcription‑quantitative PCR (RT‑qPCR) and ELISAs. Phase contrast and fluorescence microscopy were used to observe the morphology of the podocytes. The adhesive ability of HPC cells was analyzed using an attachment assay. RT‑qPCR, cyto‑immunofluorescence and western blotting were used to determine the expression levels of the adhesion‑associated genes. The expression levels of carboxypeptidases in HPC cells was also detected by RT‑qPCR. Compared with the untransfected and control virus‑transfected HPC cells, the C3a‑overexpressing cells (HPC‑C3a) failed to expand their cell bodies and develop an arborized appearance in the process of maturation, which the control cells exhibited. In addition, HPC‑C3a cells presented with decreased adhesive capacity, altered focal adhesion (FA) plaques and decreased expression of FA‑associated genes. These effects were blocked by a C3aR antagonist; however, the addition of purified C3a could not completely mimic the effects of C3a overexpression. Furthermore, HPC cells expressed carboxypeptidases, which have been reported to be able to inactivate C3a. In summary, the results demonstrated that sustained C3aR activation impaired the morphological maturation of HPC cells, which may be associated with the altered expression of FA‑associated genes and impaired FA. Since chronic complement activation has been reported in renal diseases, which indicate sustained C3aR activation in renal cells, including podocytes and podocyte progenitors, the possible role of C3aR in the dysregulation of podocyte architecture and podocyte regeneration requires further research. |
| Databáze: | OpenAIRE |
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