Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion

Roeder, Sebastian S; Barnes, Taylor J.; Lee, Jonathan S.; Kato, India; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria; Daniel, Christoph; Amann, Kerstin; Pippin, Jeffrey W.; Shankland, Stuart J.

doi:10.1016/j.kint.2016.10.015

Cited by 46 publications

(72 citation statements)

References 58 publications

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“…Similar to the studies described above [29, 30], this increase correlates with the increase in CD44 positive PECs along Bowman's capsule and the increase in activated PECs that migrated to the glomerular tuft.…”

Section: Resultssupporting

confidence: 84%

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Compound effects of aging and experimental FSGS on glomerular epithelial cells

Schneider

Eng

Kutz

et al. 2017

Aging

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Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs. Additionally, the percentage of glomeruli containing PECs with evidence of phosphorylated ERK and EMT was higher in aged FSGS mice. Extracellular matrix, measured by collagen IV and silver staining, was higher in aged FSGS mice along Bowman's capsule. However, collagen IV accumulation in the glomerular tufts alone and in glomeruli with both tuft and Bowman's capsule accumulation were similar in young FSGS and aged FSGS mice. Thus, the major difference in collagen IV staining in FSGS was along Bowman's capsule in aged mice. The significant differences in podocytes, PECs and extracellular matrixaccumulation between young mice and old mice with FSGS might explain the differences in outcomes in FSGS based on age.

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Section: Resultssupporting

confidence: 84%

“…Similarly, we have recently reported that active ERK1/2 (phospho-ERK), is an important regulator for the increase of CD44 in PECs themselves [30]. Therefore, staining for phosphorylated ERK was performed to explore ERK1/2 activation as a potential mechanism for higher CD44 and motility of PECs in aged FSGS mice.…”

Section: Resultsmentioning

confidence: 99%

Compound effects of aging and experimental FSGS on glomerular epithelial cells

Schneider

Eng

Kutz

et al. 2017

Aging

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“…A well-known marker for EMT is the alpha isoform of smooth muscle actin (SMA). ICE mice had increased SMA staining in both the OC and JM relative to Cre controls, paralleling changes seen during normal aging ( Figure 6I) (Roeder et al, 2017). Together with the in vivo data in the co-submitted manuscript (Hayano et al), these analyses indicate that the induction of non-mutagenic DSBs accelerates the DNA methylation clock and induces many of the same changes to chromatin, gene expression, and cellular identity that occur in normal mouse aging.…”

Section: F S7f and S7g)supporting

confidence: 63%

“…Two well established age-related changes in kidney are an increase in damage of the glomerular basement membrane and loss of podocytes that line the glomerular capillary. As in old wildtype mice (Roeder et al, 2017), the kidneys of treated ICE mice had fewer tissue samples that scored as normal (1+) compared to Cre controls, and a higher percent of those scored as damaged (2+ and 3+) for both the outer cortex (OC) and juxtamedullary (JM) glomerulus, along with a greater loss of podocytes (Figure 6G-H). A well-known marker for EMT is the alpha isoform of smooth muscle actin (SMA).…”

Section: F S7f and S7g)mentioning

confidence: 84%

Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals

Yang

et al. 2019

Preprint

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Short-title: Epigenetic noise and cell identity loss during agingOne Sentence Summary: The act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging 1 SUMMARY All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.2

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“…Notably, the decrease in nuclear β‐catenin was coupled to significant lowering of CD44‐positive cells, being TMA plus BL more effective than TMA plus UVA light. The reduction in CD44‐positive cells detected also in cultures treated with the compound alone may be related to the lowering of p44/42 MAPK phosphorylation, as pERK regulates CD44 expression …”

Section: Discussionmentioning

confidence: 98%