Cellular plasticity: A mechanism for homeostasis in the kidney

Assmus, Adrienne; Mullins, John J.; Brown, Cara; Mullins, L. J.

doi:10.1111/apha.13447

Cited by 20 publications

(16 citation statements)

References 119 publications

(122 reference statements)

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“…Podocyte injury is associated with several kidney diseases, such as DN, focal segmental sclerosis (FSGS), minimal change disease (MCD) and membranous glomerulonephritis (MN). 16,17 Podocyte injury causes functional and morphological alterations of podocytes, such as epithelialmesenchymal transdifferentiation, [18][19][20] hypertrophy, 21,22 detachment 23 and apoptosis. 24,25 We previously identified BASP1 as a risk factor for the progression of kidney dysfunction via podocyte injury.…”

Section: Discussionmentioning

confidence: 99%

Podocyte apoptosis in diabetic nephropathy by BASP1 activation of the p53 pathway via WT1

Zhang

et al. 2021

Acta Physiologica

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Aims: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. BASP1 (brain acid-soluble protein) is up-regulated in podocyte-specific protein phosphatase 2A knockout mice (Pod-PP2A-KO) that develop kidney dysfunction.Here, we explore the role of BASP1 for podocytes in DN. Methods: BASP1 was assessed in kidneys from DN patients and DN mouse models, podocyte specific BASP1 knockout mice (Pod-BASP1-KO mice) were generated and studied in vivo. Furthermore, podocyte injury and apoptosis were measured after BASP1 knockdown and overexpression in a mouse podocyte cell line (MPC5).Potential signalling pathways involved in podocyte apoptosis were detected. Results: BASP1 expression was up-regulated in DN patients compared to normal controls. BASP1 specific deletion in podocytes protected against podocyte injury by reducing the loss of expression of slit diaphragm molecules and foot process effacement in the DN model. BASP1 promoted actin cytoskeleton rearrangements and apoptosis in the MPC5 podocyte line. Molecules involved in the p53 pathway were down-regulated in BASP1 knockdown podocytes treated with high glucose compared to controls. BASP1 promoted podocyte apoptosis and P53 pathway activation through co-repression with Wilms' tumour 1 transcription factor (WT1). Conclusion: BASP1 activates the p53 pathway through modulation of WT1 to induce podocyte apoptosis in diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Podocyte apoptosis in diabetic nephropathy by BASP1 activation of the p53 pathway via WT1

Zhang

et al. 2021

Acta Physiologica

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“…It has been shown in the kidney that constant changes in cellular structure occur due to mechanical and chemical stimuli. When IMCD-cells were subjected to flow like it occurs during diuresis they showed altered actin cytoskeleton organization, which resulted in better viability 49 .…”

Section: Discussionmentioning

confidence: 99%

Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

Rose¹,

Kemper²,

Schwab

et al. 2021

Sci Rep

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Aquaporin-2–4 (AQP) are expressed in the principal cells of the renal collecting duct (CD). Beside their role in water transport across membranes, several studies showed that AQPs can influence the migration of cells. It is unknown whether this also applies for renal CD cells. Another fact is that the expression of these AQPs is highly modulated by the external osmolality. Here we analyzed the localization of AQP2–4 in primary cultured renal inner medullary CD (IMCD) cells and how osmolality influences the migration behavior of these cells. The primary IMCD cells showed a collective migration behavior and there were no differences in the migration speed between cells cultivated either at 300 or 600 mosmol/kg. Acute increase from 300 to 600 mosmol/kg led to a marked reduction and vice versa an acute decrease from 600 to 300 mosmol/kg to a marked increase in migration speed. Interestingly, none of the analyzed AQPs were localized at the leading edge. While AQP3 disappeared within the first 2–3 rows of cells, AQP4 was enriched at the rear end. Further analysis indicated that migration induced lysosomal degradation of AQP3. This could be prevented by activation of the protein kinase A, inducing localization of AQP3 and AQP2 at the leading edge and increasing the migration speed.

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“…While the role of Notch signaling is now well recognized for the modulation of the PC:IC ratio in the collecting duct, our study shows particular effects of disturbing Adam10 on cell polarization and cellular function that suggest a cellular dedifferentiation phenomenon. In reference to earlier reports on cellular plasticity terminology, 37 this would suggest that CD cells can “transdifferentiate” through a process of dedifferentiation into an intermediate cell type. The intermediate cell type has indeed previously been observed in adult collecting ducts.…”

Section: Discussionmentioning

confidence: 99%

Loss of Adam10 Disrupts Ion Transport in Immortalized Kidney Collecting Duct Cells

et al. 2021

Self Cite

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The kidney cortical collecting duct (CCD) comprises principal cells (PCs), intercalated cells (IC), and the recently discovered intermediate cell type. Kidney pathology in a mouse model of the syndrome of apparent aldosterone excess revealed plasticity of the CCD, with altered PC:intermediate cell:IC ratio. The self-immortalized mouse CCD cell line, mCCDcl1, shows functional characteristics of PCs, but displays a range of cell types, including intermediate cells, making it ideal to study plasticity. We knocked out Adam10, a key component of the Notch pathway, in mCCDcl1 cells, using CRISPR-Cas9 technology, and isolated independent clones, which exhibited severely affected sodium transport capacity and loss of aldosterone response. Single-cell RNA sequencing revealed significantly reduced expression of major PC-specific markers, such as Scnn1g (γ-ENaC) and Hsd11b2 (11βHSD2), but no significant changes in transcription of components of the Notch pathway were observed. Immunostaining in the knockout clone confirmed the decrease in expression of γ-ENaC and importantly, showed an altered, diffuse distribution of PC and IC markers, suggesting altered trafficking in the Adam10 knockout clone as an explanation for the loss of polarization.

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Cellular plasticity: A mechanism for homeostasis in the kidney

Cited by 20 publications

References 119 publications

Podocyte apoptosis in diabetic nephropathy by BASP1 activation of the p53 pathway via WT1

Podocyte apoptosis in diabetic nephropathy by BASP1 activation of the p53 pathway via WT1

Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

Loss of Adam10 Disrupts Ion Transport in Immortalized Kidney Collecting Duct Cells

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