Open Access

Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells

  • Authors:
    • Jing‑Min Zheng
    • Sha‑Sha Wang
    • Xiong Tian
    • De‑Jun Chen
  • View Affiliations

  • Published online on: October 22, 2020     https://doi.org/10.3892/mmr.2020.11626
  • Pages: 5326-5338
  • Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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December-2020
Volume 22 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zheng JM, Wang SS, Tian X and Chen DJ: Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells . Mol Med Rep 22: 5326-5338, 2020
APA
Zheng, J., Wang, S., Tian, X., & Chen, D. (2020). Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells . Molecular Medicine Reports, 22, 5326-5338. https://doi.org/10.3892/mmr.2020.11626
MLA
Zheng, J., Wang, S., Tian, X., Chen, D."Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells ". Molecular Medicine Reports 22.6 (2020): 5326-5338.
Chicago
Zheng, J., Wang, S., Tian, X., Chen, D."Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells ". Molecular Medicine Reports 22, no. 6 (2020): 5326-5338. https://doi.org/10.3892/mmr.2020.11626