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Article ; Online: The loss of profilin1 is catastrophic to podocytes.

Mallipattu, Sandeep K

2023 Volume 133, Issue 24

Abstract: Profilin1 belongs to a family of small monomeric actin-binding proteins with diverse roles in fundamental actin-dependent cellular processes required for cell survival. Podocytes are postmitotic visceral epithelial cells critical for the structure and ... ...

Abstract	Profilin1 belongs to a family of small monomeric actin-binding proteins with diverse roles in fundamental actin-dependent cellular processes required for cell survival. Podocytes are postmitotic visceral epithelial cells critical for the structure and function of the kidney filtration barrier. There is emerging evidence that the actin-related mode of cell death known as mitotic catastrophe is an important pathway involved in podocyte loss. In this issue of the JCI, Tian, Pedigo, and colleagues demonstrate that profilin1 deficiency in podocytes triggered cell cycle reentry, resulting in abortive cytokinesis with a loss in ribosomal RNA processing that leads to podocyte loss and glomerulosclerosis. This study demonstrates the essential role of actin dynamics in mediating this fundamental mode of podocyte cell death.
MeSH term(s)	Humans ; Podocytes/metabolism ; Actins/metabolism ; Kidney Diseases/metabolism ; Cell Cycle ; Cell Death
Chemical Substances	Actins
Language	English
Publishing date	2023-12-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI175594
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Article ; Online: Central role of podocytes in mediating cellular cross talk in glomerular health and disease.

Gujarati, Nehaben A / Chow, Andrew K / Mallipattu, Sandeep K

American journal of physiology. Renal physiology

2024 Volume 326, Issue 3, Page(s) F313–F325

Abstract: Podocytes are highly specialized epithelial cells that surround the capillaries of the glomeruli in the kidney. Together with the glomerular endothelial cells, these postmitotic cells are responsible for regulating filtrate from the circulating blood ... ...

Abstract	Podocytes are highly specialized epithelial cells that surround the capillaries of the glomeruli in the kidney. Together with the glomerular endothelial cells, these postmitotic cells are responsible for regulating filtrate from the circulating blood with their organized network of interdigitating foot processes that wrap around the glomerular basement membrane. Although podocyte injury and subsequent loss is the hallmark of many glomerular diseases, recent evidence suggests that the cell-cell communication between podocytes and other glomerular and nonglomerular cells is critical for the development and progression of kidney disease. In this review, we highlight these key cellular pathways of communication and how they might be a potential target for therapy in glomerular disease. We also postulate that podocytes might serve as a central hub for communication in the kidney under basal conditions and in response to cellular stress, which may have implications for the development and progression of glomerular diseases.
MeSH term(s)	Humans ; Podocytes/metabolism ; Endothelial Cells ; Kidney Diseases/metabolism ; Kidney ; Glomerular Basement Membrane/metabolism
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00328.2023
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Article ; Online: Dialysis resource allocation in critical care: the impact of the COVID-19 pandemic and the promise of big data analytics.

Koraishy, Farrukh M / Mallipattu, Sandeep K

Frontiers in nephrology

2023 Volume 3, Page(s) 1266967

Abstract: The COVID-19 pandemic resulted in an unprecedented burden on intensive care units (ICUs). With increased demands and limited supply, critical care resources, including dialysis machines, became scarce, leading to the undertaking of value-based cost- ... ...

Abstract	The COVID-19 pandemic resulted in an unprecedented burden on intensive care units (ICUs). With increased demands and limited supply, critical care resources, including dialysis machines, became scarce, leading to the undertaking of value-based cost-effectiveness analyses and the rationing of resources to deliver patient care of the highest quality. A high proportion of COVID-19 patients admitted to the ICU required dialysis, resulting in a major burden on resources such as dialysis machines, nursing staff, technicians, and consumables such as dialysis filters and solutions and anticoagulation medications. Artificial intelligence (AI)-based big data analytics are now being utilized in multiple data-driven healthcare services, including the optimization of healthcare system utilization. Numerous factors can impact dialysis resource allocation to critically ill patients, especially during public health emergencies, but currently, resource allocation is determined using a small number of traditional factors. Smart analytics that take into account all the relevant healthcare information in the hospital system and patient outcomes can lead to improved resource allocation, cost-effectiveness, and quality of care. In this review, we discuss dialysis resource utilization in critical care, the impact of the COVID-19 pandemic, and how AI can improve resource utilization in future public health emergencies. Research in this area should be an important priority.
Language	English
Publishing date	2023-10-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2813-0626
ISSN (online)	2813-0626
DOI	10.3389/fneph.2023.1266967
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Article ; Online: Transcriptional regulation of proximal tubular metabolism in acute kidney injury.

Piret, Sian E / Mallipattu, Sandeep K

Pediatric nephrology (Berlin, Germany)

2022 Volume 38, Issue 4, Page(s) 975–986

Abstract: The kidney, and in particular the proximal tubule (PT), has a high demand for ATP, due to its function in bulk reabsorption of solutes. In normal PT, ATP levels are predominantly maintained by fatty acid β-oxidation (FAO), the tricarboxylic acid (TCA) ... ...

Abstract	The kidney, and in particular the proximal tubule (PT), has a high demand for ATP, due to its function in bulk reabsorption of solutes. In normal PT, ATP levels are predominantly maintained by fatty acid β-oxidation (FAO), the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. The normal PT also undertakes gluconeogenesis and metabolism of amino acids. Acute kidney injury (AKI) results in profound PT metabolic alterations, including suppression of FAO, gluconeogenesis, and metabolism of some amino acids, and upregulation of glycolytic enzymes. Recent studies have elucidated new transcriptional mechanisms regulating metabolic pathways in normal PT, as well as the metabolic switch in AKI. A number of transcription factors have been shown to play important roles in FAO, which are themselves downregulated in AKI, while hypoxia-inducible factor 1α, which is upregulated in ischemia-reperfusion injury, is a likely driver of the upregulation of glycolytic enzymes. Transcriptional regulation of amino acid metabolic pathways is less well understood, except for catabolism of branched-chain amino acids, which is likely suppressed in AKI by upregulation of Krüppel-like factor 6. This review will focus on the transcriptional regulation of specific metabolic pathways in normal PT and in AKI, as well as highlighting some of the gaps in knowledge and challenges that remain to be addressed.
MeSH term(s)	Humans ; Acute Kidney Injury/genetics ; Acute Kidney Injury/metabolism ; Kidney/metabolism ; Kidney Tubules, Proximal/metabolism ; Reperfusion Injury/metabolism ; Amino Acids/metabolism ; Adenosine Triphosphate/metabolism
Chemical Substances	Amino Acids ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2022-10-01
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-022-05748-2
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Article ; Online: Monitoring Hospitalized Dialysis Patients With COVID-19: Repurposing Baby Monitors for Patient and Staff Safety.

Khan, Sobia / Mallipattu, Sandeep K

Kidney medicine

2020 Volume 3, Issue 1, Page(s) 136–138

Language	English
Publishing date	2020-12-10
Publishing country	United States
Document type	Journal Article
ISSN	2590-0595
ISSN (online)	2590-0595
DOI	10.1016/j.xkme.2020.10.004
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Article ; Online: Proximal Tubular Transcription Factors in Acute Kidney Injury: Recent Advances.

Piret, Sian E / Mallipattu, Sandeep K

Nephron

2020 Volume 144, Issue 12, Page(s) 613–615

Abstract: The proximal tubule (PT) is a major target in acute kidney injury (AKI), leading to profound changes in PT cell biology. Amongst the genes with early and robust changes in expression are many transcription factors (TFs), which themselves account for ... ...

Abstract	The proximal tubule (PT) is a major target in acute kidney injury (AKI), leading to profound changes in PT cell biology. Amongst the genes with early and robust changes in expression are many transcription factors (TFs), which themselves account for other transcriptomic changes. Potentially important TFs are being revealed in large sequencing datasets; however, to understand whether these TFs account for adaptive or maladaptive changes requires further mechanistic studies, which may reveal novel therapeutic targets. This mini review will highlight the identification and biology of 3 novel TFs in AKI: Sox9, Foxm1, and Foxo3.
MeSH term(s)	Acute Kidney Injury/metabolism ; Humans ; Kidney Tubules, Proximal/metabolism ; Transcription Factors/metabolism
Chemical Substances	Transcription Factors
Language	English
Publishing date	2020-07-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000508856
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Article ; Online: The Role of Podocytes and Podocyte-Associated Biomarkers in Diagnosis and Treatment of Diabetic Kidney Disease.

Kravets, Igor / Mallipattu, Sandeep K

Journal of the Endocrine Society

2020 Volume 4, Issue 4, Page(s) bvaa029

Abstract: Diabetic kidney disease (DKD) is an important public health problem. Podocyte injury is a central event in the mechanism of DKD development. Podocytes are terminally differentiated, highly specialized glomerular visceral epithelial cells critical for the ...

Abstract	Diabetic kidney disease (DKD) is an important public health problem. Podocyte injury is a central event in the mechanism of DKD development. Podocytes are terminally differentiated, highly specialized glomerular visceral epithelial cells critical for the maintenance of the glomerular filtration barrier. Although potential mechanisms by which diabetic milieu contributes to irreversible loss of podocytes have been described, identification of markers that prognosticate either the development of DKD or the progression to end-stage kidney disease (ESKD) have only recently made it to the forefront. Currently, the most common marker of early DKD is microalbuminuria; however, this marker has significant limitations: not all diabetic patients with microalbuminuria will progress to ESKD and as many as 30% of patients with DKD have normal urine albumin levels. Several novel biomarkers indicating glomerular or tubular damage precede microalbuminuria, suggesting that the latter develops when significant kidney injury has already occurred. Because podocyte injury plays a key role in DKD pathogenesis, identification of markers of early podocyte injury or loss may play an important role in the early diagnosis of DKD. Such biomarkers in the urine include podocyte-released microparticles as well as expression of podocyte-specific markers. Here, we review the mechanisms by which podocyte injury contributes to DKD as well as key markers that have been recently implicated in the development and/or progression of DKD and might serve to identify individuals that require earlier preventative care and treatment in order to slow the progression to ESKD.
Language	English
Publishing date	2020-03-05
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvaa029
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Article: Recent Advances in Kidney Bioengineering.

Cintron Pregosin, Nina / Bronstein, Robert / Mallipattu, Sandeep K

Frontiers in pediatrics

2021 Volume 9, Page(s) 743301

Abstract: Kidney disease is an epidemic that affects more than 600 million people worldwide. The socioeconomic impacts of the disease disproportionately affect Hispanic and non-Hispanic Black Americans, making the disease an issue of social inequality. The urgency ...

Abstract	Kidney disease is an epidemic that affects more than 600 million people worldwide. The socioeconomic impacts of the disease disproportionately affect Hispanic and non-Hispanic Black Americans, making the disease an issue of social inequality. The urgency of this situation has only become worse during the COVID-19 pandemic, as those who are hospitalized for COVID-19 have an increased risk of kidney failure. For researchers, the kidney is a complex organ that is difficult to accurately model and understand. Traditional cell culture models are not adequate for studying the functional intricacies of the kidney, but recent experiments have offered improvements for understanding these systems. Recent progress includes organoid modeling, 3D bioprinting, decellularization, and microfluidics. Here, we offer a review of the most recent advances in kidney bioengineering.
Language	English
Publishing date	2021-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2021.743301
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Article ; Online: Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease.

Bronstein, Robert / Pace, Jesse / Gowthaman, Yogesh / Salant, David J / Mallipattu, Sandeep K

Journal of the American Society of Nephrology : JASN

2023 Volume 34, Issue 5, Page(s) 737–750

Abstract: Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer ... ...

Abstract	Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule. Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation-occurring immediately before the emergence of the fully mature nephron. These two cell types, therefore, share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatiotemporal gene expression zone between podocytes and PECs. In addition to their homeostatic functions, podocytes and PECs also have roles in kidney pathogenesis. Rapid podocyte loss in diseases, such as rapidly progressive GN and collapsing and cellular subtypes of FSGS, is closely allied with PEC proliferation and migration toward the capillary tuft, resulting in the formation of crescents and pseudocrescents. PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell types during development and in various manifestations of kidney pathology is the primary focus of this review.
MeSH term(s)	Humans ; Podocytes/metabolism ; Glomerulosclerosis, Focal Segmental/pathology ; Kidney Glomerulus/pathology ; Bowman Capsule/metabolism ; Bowman Capsule/pathology ; Epithelial Cells/metabolism
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.0000000000000104
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Article ; Online: Single-Cell Spatial MIST for Versatile, Scalable Detection of Protein Markers.

Meah, Arafat / Vedarethinam, Vadanasundari / Bronstein, Robert / Gujarati, Nehaben / Jain, Tanya / Mallipattu, Sandeep K / Li, Yueming / Wang, Jun

Biosensors

2023 Volume 13, Issue 9

Abstract: High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ ...

Abstract	High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ tagging (MIST) transfers the spatial protein expression information to an ultrahigh-density, large-scale MIST array. This technique has been optimized to reach single-cell resolution by adoption of smaller array units and 30% 8-arm PEG polymer as transfer medium. Tissue cell nuclei stained with lamin B have been clearly visualized on the MIST arrays and are colocalized with detection of nine mouse brain markers. Pseudocells defined at 10 μm in size have been used to fully profile tissue regions including cells and the intercellular space. We showcased the versatility of our technology by successfully detecting 20 marker proteins in kidney samples with the addition of five minutes atop the duration of standard immunohistochemistry protocols. Spatial MIST is amenable to iterative staining and detection on the same tissue samples. When 25 proteins were co-detected on 1 mouse brain section for each round and 5 rounds were executed, an ultrahigh multiplexity of 125 proteins was obtained for each pseudocell. With its unique abilities, this single-cell spatial MIST technology has the potential to become an important method in advanced diagnosis of complex diseases.
MeSH term(s)	Animals ; Mice ; Cell Nucleus ; Exobiology ; Extracellular Space ; Kidney ; Polymers ; Skin Neoplasms
Chemical Substances	Polymers
Language	English
Publishing date	2023-08-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios13090852
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