Albumin-induced Premature Senescence in Human Renal Proximal Tubular Cells and Its Relationship with Intercellular Fibrosis

Overview

Journal Acta Biochim Biophys Sin (Shanghai)

Specialties Biochemistry
Biophysics

Date 2022 Jun 17

PMID 35713317

Authors

Wen Lu

Shijing Ren

Wenhui Dong

Xiaomin Li

Zongji Zheng

Yijie Jia

Yaoming Xue

Affiliations

Soon will be listed here.

Abstract

The presence of senescent cells is associated with renal fibrosis. This study aims to investigate the effect of albumin-induced premature senescence on tubulointerstitial fibrosis and its possible mechanism . Different concentrations of bovine serum albumim (BSA) with or without si-p21 are used to stimulate HK-2 cells for 72 h, and SA-β-gal activity, senescence-associated secretory phenotypes (SASPs), LaminB1 are used as markers of senescence. Immunofluorescence staining is performed to characterize the G2/M phase arrest between the control and BSA groups. Alterations in the DNA damage marker γ-H2AX, fibrogenesis, and associated proteins at the G2/M phase, such as p21, p-CDC25C and p-CDK1, are evaluated. Compared with those in the control group, the SA-β-gal activity, SASP, and γ-H2AX levels are increased in the BSA group, while the level of LaminB1 is decreased. Meanwhile, HK-2 cells blocked at the G2/M phase are significantly increased under the stimulation of BSA, and the levels of p21, p-CDC25C and p-CDK1, as well as fibrogenesis are also increased. When p21 expression is inhibited, the levels of p-CDC25C and p-CDK1 are decreased and the G2/M phase arrest is improved, which decreases the production of fibrogenesis. In conclusion, BSA induces renal tubular epithelial cell premature senescence, which regulates the G2/M phase through the CDC25C/CDK1 pathway, leading to tubulointerstitial fibrosis.

Citing Articles

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