Identification of common and differential mechanisms of glomerulus and tubule senescence in 24-month-old rats by quantitative LC-MS/MS

Abstract

Kidney aging together with related renal disease had become a major clinical problem. Understanding the mechanisms of aging was important for suspending senescence and decreasing the incidence of aging-related diseases. In the present work, 24-month-old F344 rats were used as aging rats and 3-month-old rats were used as young controls. Senescence-associated-β-galactosidase staining results showed that the degree of senescence in renal tubules was more severe than that in glomeruli. We performed quantitative LC-MS to assess the differential protein expression profiles of senescent glomeruli and tubules. Bioinformatics analysis showed that aging, response to oxidative stress, nucleotide metabolism, amine acid metabolism, and inflammatory response were common mechanisms of glomerulus and tubule senescence. Differentially expressed proteins network mediated Golgi vesicle transport, actin filament based process, and regulation of cell death were associated with tubule senescence. More importantly, we found that the changes of four and a half LIM protein 2 (FHL2) were opposite in senescent glomeruli and tubules, and FHL2 could regulate p16 by suppressing T-box 3, which was involved in regulation of senescence in glomeruli and tubules. In conclusion, we assessed the mechanisms of senescence in aging glomeruli and tubules, and the results yielded new insight into kidney senescence.

A cmap-enabled gene expression signature-matching approach identifies small-molecule inducers of accelerated cell senescence

“…Building on the pioneering studies that identified common senescence markers such as p21 and/or p16 and SA-βGal, several prior system biology-based efforts to discover signatures of senescence have applied transcriptomics or proteomics to examine replicative senescence [41, 42] and accelerated senescence [43] in cancer cells and in aging organs of human or animals [8, 9]. While these studies have revealed the common pattern of activation of inflammatory pathways linked to the SASP [10, 11, 44, 45], the gene expression patterns that underlie other characteristic features of senescence have remained largely obscure.…”

“…Programmed senescence is a recently described feature of early development [7]. Common features of these diverse forms of senescence include enlarged cell size, unrepaired genomic damage, proliferative arrest linked to expression of the p21 CIP/WAF1 and/or p16 Ink4A stoichiometric cyclin-dependent kinase inhibitors, and activation of senescence-associated β-galactosidase activity (SA-β-Gal) [8–12].…”

Quantitative Proteomics Analysis of Sporadic Medullary Thyroid Cancer Reveals FN1 as a Potential Novel Candidate Prognostic Biomarker

“…The labeled fractions were analyzed using the Lumos mass spectrometer as described previously . For details, see supplemental online Appendix 1.…”

The different expression of glycogen phosphorylases in renal clear cell renal carcinoma and chromophobe renal carcinoma

“…The data analysis was similar to that described in a previous study [8]. Proteome Discoverer from UniProt (version PD1.4, Thermo-Fisher Scientific) was used to analyze the raw data with the human database.…”

“…The tumors and adjacent normal tissues were ground with liquid nitrogen in a mortar and dissolved in fresh lysis buffer (8 M urea in PBS, pH 8-8.5, 1 mM PMSF, and 1 mM protease inhibitor cocktail). The digestion process was similar to that used in a previous study [8]. Briefly, protein content was determined using the BCA Protein Assay Kit (Thermo-Fisher Scientific, Rockford, IL, USA), in accordance with the manufacturer's instructions.…”