The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals
Issued Date
2024-01-01
Resource Type
eISSN
2666027X
Scopus ID
2-s2.0-85180773574
Journal Title
Current Research in Toxicology
Volume
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Current Research in Toxicology Vol.6 (2024)
Suggested Citation
Hadpech S., Peerapen P., Thongboonkerd V. The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals. Current Research in Toxicology Vol.6 (2024). doi:10.1016/j.crtox.2023.100145 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/95623
Title
The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals
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Abstract
Calcium oxalate monohydrate (COM), the most important crystal causing kidney stone disease, upregulates lamin A/C but downregulates zonula occludens-1 (ZO-1) in renal tubular cells. While roles for F-actin and α-tubulin and their association with ZO-1 are known to regulate COM-mediated tight junction (TJ) disruption, roles of lamin A/C and its interplay with ZO-1 in COM kidney stone model remain unclear and are thus the objectives of this study. Lamin A/C was knocked down in MDCK cells by silencing RNA specific for LMNA (siLMNA). Both wild-type (WT) and siLMNA cells were treated with COM for 48-h compared with the untreated (control) cells. Western blotting and immunofluorescence staining revealed upregulated lamin A/C and downregulated ZO-1 in the COM-treated WT cells. siLMNA successfully reduced lamin A/C expression in both control and COM-treated cells. Nonetheless, siLMNA did not reverse the effect of COM on the decreases in ZO-1 and transepithelial resistance, but further reduced their levels in both control and COM-treated cells. Protein-protein interaction analysis demonstrated that two cytoskeletal proteins (actin and tubulin) served as the linkers to connect lamin A/C with ZO-1 and occludin (both of which are the TJ proteins). Altogether, these data implicate that lamin A/C and ZO-1 are indirectly associated to control TJ function, and ZO-1 expression is regulated by lamin A/C. Moreover, COM-induced upregulation of lamin A/C most likely serves as a compensatory mechanism to cope with the downregulation of ZO-1 during COM-mediated TJ disruption.