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Article ; Online: Cannabinoid receptor type 1 activation causes a water diuresis by inducing an acute central diabetes insipidus in mice.

Rein, Joshua L / Mackie, Ken / Kleyman, Thomas R / Satlin, Lisa M

American journal of physiology. Renal physiology

2024 Volume 326, Issue 6, Page(s) F917–F930

Abstract: Cannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, ... ...

Abstract	Cannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids, which are endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled aquaporin 2 (AQP2)-negative cells in the cortical and medullary CD and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we used a clearance approach in mice that were acid loaded with 280 mM NH
MeSH term(s)	Animals ; Receptor, Cannabinoid, CB1/metabolism ; Diuresis/drug effects ; Benzoxazines/pharmacology ; Kidney Tubules, Collecting/metabolism ; Kidney Tubules, Collecting/drug effects ; Aquaporin 2/metabolism ; Morpholines/pharmacology ; Naphthalenes/pharmacology ; Male ; Diabetes Insipidus, Neurogenic/metabolism ; Diabetes Insipidus, Neurogenic/physiopathology ; Mice, Inbred C57BL ; Cannabinoid Receptor Agonists/pharmacology ; Mice ; Disease Models, Animal
Chemical Substances	Receptor, Cannabinoid, CB1 ; Benzoxazines ; Aquaporin 2 ; (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone (5H31GI9502) ; Morpholines ; Naphthalenes ; Cannabinoid Receptor Agonists ; CNR1 protein, mouse ; Aqp2 protein, mouse
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00320.2022
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Article ; Online: Navigating the kidney organoid: insights into assessment and enhancement of nephron function.

Tabibzadeh, Nahid / Satlin, Lisa M / Jain, Sanjay / Morizane, Ryuji

American journal of physiology. Renal physiology

2023 Volume 325, Issue 6, Page(s) F695–F706

Abstract: Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, ...

Abstract	Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, drug discovery, and regenerative medicine, the functional capacity of kidney organoids has emerged as a critical question in the field. Kidney organoids produced using several protocols harbor key structures of native kidneys. Here, we review the current state, recent advances, and future challenges in the functional characterization of kidney organoids, strategies to accelerate and enhance kidney organoid functions, and access to PSC resources to advance organoid research. The strategies to construct physiologically relevant kidney organoids include the use of organ-on-a-chip technologies that integrate fluid circulation and improve organoid maturation. These approaches result in increased expression of the major tubular transporters and elements of mechanosensory signaling pathways suggestive of improved functionality. Nevertheless, continuous efforts remain crucial to create kidney tissue that more faithfully replicates physiological conditions for future applications in kidney regeneration medicine and their ethical use in patient care.
MeSH term(s)	Animals ; Humans ; Kidney/physiology ; Regeneration ; Nephrons ; Pluripotent Stem Cells ; Organoids/metabolism ; Mammals
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00166.2023
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Article ; Online: Kcnma1

Whelan, Sarah Christine M / Mutchler, Stephanie M / Han, Agnes / Priestley, Catherine / Satlin, Lisa M / Kleyman, Thomas R / Shi, Shujie

American journal of physiology. Renal physiology

2024

Abstract: The pore-forming α subunit of the large conductance potassium (BK) channel is encoded by a single gene, ...

Abstract	The pore-forming α subunit of the large conductance potassium (BK) channel is encoded by a single gene,
Language	English
Publishing date	2024-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00100.2024
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Article ; Online: Functional maturation of kidney organoid tubules: PIEZO1-mediated Ca

Carrisoza-Gaytan, Rolando / Kroll, Katharina T / Hiratsuka, Ken / Gupta, Navin R / Morizane, Ryuji / Lewis, Jennifer A / Satlin, Lisa M

American journal of physiology. Cell physiology

2023 Volume 324, Issue 3, Page(s) C757–C768

Abstract: ... Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T ...

Abstract	Kidney organoids cultured on adherent matrices in the presence of superfusate flow generate vascular networks and exhibit more mature podocyte and tubular compartments compared with static controls (Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T, Bonventre JV, Lewis JA, Morizane R.
MeSH term(s)	Animals ; Mice ; Calcium/metabolism ; Fura-2 ; Ion Channels/metabolism ; Kidney/metabolism ; Kidney Tubules/metabolism ; Calcium Signaling
Chemical Substances	Calcium (SY7Q814VUP) ; Fura-2 (TSN3DL106G) ; Ion Channels ; Piezo1 protein, mouse
Language	English
Publishing date	2023-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00288.2022
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Article ; Online: Expression and localization of the mechanosensitive/osmosensitive ion channel TMEM63B in the mouse urinary tract.

Dalghi, Marianela G / DuRie, Ella / Ruiz, Wily G / Clayton, Dennis R / Montalbetti, Nicolas / Mutchler, Stephanie B / Satlin, Lisa M / Kleyman, Thomas R / Carattino, Marcelo D / Shi, Yun Stone / Apodaca, Gerard

Physiological reports

2024 Volume 12, Issue 9, Page(s) e16043

Abstract: The epithelial cells that line the kidneys and lower urinary tract are exposed to mechanical forces including shear stress and wall tension; however, the mechanosensors that detect and respond to these stimuli remain obscure. Candidates include the OSCA/ ... ...

Abstract	The epithelial cells that line the kidneys and lower urinary tract are exposed to mechanical forces including shear stress and wall tension; however, the mechanosensors that detect and respond to these stimuli remain obscure. Candidates include the OSCA/TMEM63 family of ion channels, which can function as mechanosensors and osmosensors. Using Tmem63b
MeSH term(s)	Animals ; Female ; Male ; Mice ; Calcium Channels/genetics ; Calcium Channels/metabolism ; Epithelial Cells/metabolism ; Mechanotransduction, Cellular/physiology ; Mice, Inbred C57BL ; Urinary Tract/metabolism ; Urothelium/metabolism ; Urothelium/cytology
Chemical Substances	Calcium Channels
Language	English
Publishing date	2024-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.16043
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Article ; Online: PIEZO1 is a distal nephron mechanosensor and is required for flow-induced K+ secretion.

Carrisoza-Gaytan, Rolando / Mutchler, Stephanie M / Carattino, Francisco / Soong, Joanne / Dalghi, Marianela G / Wu, Peng / Wang, WenHui / Apodaca, Gerard / Satlin, Lisa M / Kleyman, Thomas R

The Journal of clinical investigation

2024 Volume 134, Issue 5

Abstract: Ca2+-activated BK channels in renal intercalated cells (ICs) mediate luminal flow-induced K+ secretion (FIKS), but how ICs sense increased flow remains uncertain. We examined whether PIEZO1, a mechanosensitive Ca2+-permeable channel expressed in the ... ...

Abstract	Ca2+-activated BK channels in renal intercalated cells (ICs) mediate luminal flow-induced K+ secretion (FIKS), but how ICs sense increased flow remains uncertain. We examined whether PIEZO1, a mechanosensitive Ca2+-permeable channel expressed in the basolateral membranes of ICs, is required for FIKS. In isolated cortical collecting ducts (CCDs), the mechanosensitive cation-selective channel inhibitor GsMTx4 dampened flow-induced increases in intracellular Ca2+ concentration ([Ca2+]i), whereas the PIEZO1 activator Yoda1 increased [Ca2+]i and BK channel activity. CCDs from mice fed a high-K+ (HK) diet exhibited a greater Yoda1-dependent increase in [Ca2+]i than CCDs from mice fed a control K+ diet. ICs in CCDs isolated from mice with a targeted gene deletion of Piezo1 in ICs (IC-Piezo1-KO) exhibited a blunted [Ca2+]i response to Yoda1 or increased flow, with an associated loss of FIKS in CCDs. Male IC-Piezo1-KO mice selectively exhibited an increased blood [K+] in response to an oral K+ bolus and blunted urinary K+ excretion following a volume challenge. Whole-cell expression of BKα subunit was reduced in ICs of IC-Piezo1-KO mice fed an HK diet. We conclude that PIEZO1 mediates flow-induced basolateral Ca2+ entry into ICs, is upregulated in the CCD in response to an HK diet, and is necessary for FIKS.
MeSH term(s)	Male ; Mice ; Animals ; Kidney Tubules, Collecting/metabolism ; Large-Conductance Calcium-Activated Potassium Channels/genetics ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Calcium/metabolism ; Nephrons/metabolism ; Kidney/metabolism ; Ion Channels/genetics ; Ion Channels/metabolism
Chemical Substances	Large-Conductance Calcium-Activated Potassium Channels ; Calcium (SY7Q814VUP) ; Piezo1 protein, mouse ; Ion Channels
Language	English
Publishing date	2024-03-01
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/JCI174806
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Article: Proteolytic Cleavage of the ENaC γ Subunit - Impact Upon Na

Ray, Evan C / Nickerson, Andrew / Sheng, Shaohu / Carrisoza-Gaytan, Rolando / Lam, Tracey / Marciszyn, Allison / Zhang, Lei / Jordahl, Alexa / Bi, Chunming / Winfrey, Aaliyah / Kou, Zhaohui / Gingras, Sebastien / Kirabo, Annet / Satlin, Lisa M / Kleyman, Thomas R

bioRxiv : the preprint server for biology

2024

Abstract: The ENaC gamma subunit is essential for homeostasis of ... ...

Abstract	The ENaC gamma subunit is essential for homeostasis of Na
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.12.579964
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Article ; Online: Influence of proteolytic cleavage of ENaC's γ subunit upon Na

American journal of physiology. Renal physiology

2024 Volume 326, Issue 6, Page(s) F1066–F1077

Abstract: The epithelial ... ...

Abstract	The epithelial Na
MeSH term(s)	Animals ; Epithelial Sodium Channels/metabolism ; Epithelial Sodium Channels/genetics ; Male ; Female ; Sodium/metabolism ; Proteolysis ; Kidney Tubules, Collecting/metabolism ; Homeostasis ; Furin/metabolism ; Furin/genetics ; Mice ; Colon/metabolism ; Potassium/metabolism ; Diet, Sodium-Restricted ; Mice, 129 Strain ; Mutation ; Amiloride/pharmacology
Chemical Substances	Epithelial Sodium Channels ; Scnn1g protein, mouse ; Sodium (9NEZ333N27) ; Furin (EC 3.4.21.75) ; Potassium (RWP5GA015D) ; Amiloride (7DZO8EB0Z3)
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00027.2024
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Article: Mineralocorticoid receptor-independent activation of ENaC in bile duct ligated mice.

Wang, Xue-Ping / Mutchler, Stephanie M / Carrisoza-Gáytan, Rolando / Al-Bataineh, Mohammad / Baty, Catherine J / Vandevender, Amber / Srinivasan, Priyanka / Tan, Roderick J / Jurczak, Michael J / Satlin, Lisa M / Kashlan, Ossama B

bioRxiv : the preprint server for biology

2023

Abstract: Sodium and fluid retention in liver disease is classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). Aldosterone dives ... ...

Abstract	Sodium and fluid retention in liver disease is classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). Aldosterone dives Na
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.19.558474
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Article: Live functional assays reveal longitudinal maturation of transepithelial transport in kidney organoids.

Rizki-Safitri, Astia / Gupta, Navin / Hiratsuka, Ken / Kobayashi, Kenichi / Zhang, Chengcheng / Ida, Kazumi / Satlin, Lisa M / Morizane, Ryuji

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 978888

Abstract: Kidney organoids derived from hPSCs have opened new opportunities to develop kidney models for preclinical studies and immunocompatible kidney tissues for regeneration. Organoids resemble native nephrons that consist of filtration units and tubules, yet ... ...

Abstract	Kidney organoids derived from hPSCs have opened new opportunities to develop kidney models for preclinical studies and immunocompatible kidney tissues for regeneration. Organoids resemble native nephrons that consist of filtration units and tubules, yet little is known about the functional capacity of these organoid structures. Transcriptomic analyses provide insight into maturation and transporter activities that represent kidney functions. However, functional assays in organoids are necessary to demonstrate the activity of these transport proteins in live tissues. The three-dimensional (3D) architecture adds complexity to real-time assays in kidney organoids. Here, we develop a functional assay using live imaging to assess transepithelial transport of rhodamine 123 (Rh123), a fluorescent substrate of P-glycoprotein (P-gp), in organoids affixed to coverslip culture plates for accurate real-time observation. The identity of organoid structures was probed using Lotus Tetragonolobus Lectin (LTL), which binds to glycoproteins present on the surface of proximal tubules. Within 20 min of the addition of Rh123 to culture media, Rh123 accumulated in the tubular lumen of organoids. Basolateral-to-apical accumulation of the dye/marker was reduced by pharmacologic inhibition of MDR1 or OCT2, and OCT2 inhibition reduced the Rh123 uptake. The magnitude of Rh123 transport was maturation-dependent, consistent with MDR1 expression levels assessed by RNA-seq and immunohistochemistry. Specifically, organoids on day 21 exhibit less accumulation of Rh123 in the lumen unlike later-stage organoids from day 30 of differentiation. Our work establishes a live functional assessment in 3D kidney organoids, enabling the functional phenotyping of organoids in health and disease.
Language	English
Publishing date	2022-08-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.978888
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