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Nesfatin-1 mitigates calcium oxalate nephropathy in mice through GPR12 receptor modulation and PKCα/NADPH oxidase pathway inhibition.

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Τίτλος: Nesfatin-1 mitigates calcium oxalate nephropathy in mice through GPR12 receptor modulation and PKCα/NADPH oxidase pathway inhibition.
Συγγραφείς: Lahane GP; Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India., Bhat A; Department of Life Science, Central University of Karnataka, Kalaburagi, 585367, India., Kulkarni O; Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India., Dhar A; Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India. Electronic address: artidhar@hyderabad.bits-pilani.ac.in.
Πηγή: Life sciences [Life Sci] 2026 Oct 01; Vol. 402, pp. 124544. Date of Electronic Publication: 2026 Jun 23.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
Imprint Name(s): Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
Ιατρικοί όροι (MeSH): Nucleobindins*/metabolism , Nucleobindins*/pharmacology , NADPH Oxidases*/metabolism , Nephrolithiasis*/metabolism , Nephrolithiasis*/pathology , Nephrolithiasis*/chemically induced , Protein Kinase C-alpha*/metabolism , Receptors, G-Protein-Coupled*/metabolism , Calcium Oxalate*/toxicity , Calcium Oxalate*/metabolism, Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Apoptosis
Περίληψη: Aims: Nephrolithiasis, a prevalent and recurring kidney disease is associated with oxidative stress, inflammation, apoptosis, necroptosis, and fibrosis. Nesfatin-1, a bioactive peptide, is known to have antioxidant, anti-inflammatory, and antifibrotic properties, however, its role in nephrolithiasis associated pathological changes remains unexplored. Moreover, the receptor by which nesfatin-1 exerts its protective effects is unknown. Thus, the present study aimed to elucidate the role and underlying molecular mechanisms of nesfatin-1 in a mouse model of glyoxylate-induced nephrolithiasis/nephrocalcinosis.
Materials and Methods: Mouse model of nephrolithiasis was created via administration of glyoxylate, and cell injury models of tubular epithelial cells were done using calcium oxalate monohydrate (COM). Kidney function, histopathology, oxidative stress, inflammation, apoptosis, and renal interstitial fibrosis were measured using assay kits, confocal microscopy and protein/mRNA expression analysis. Moreover, co-immunoprecipitation was performed to investigate the receptors involved and underlying molecular mechanism.
Key Findings: Nephrolithiasis mice showed reduced nesfatin-1 expression and elevated markers of kidney damage, including, histological abnormalities, inflammation, necroptosis, and fibrosis. Mechanistically, nesfatin-1 modulated the GPR 12 oligomerization and inhibited the COM-induced PKCα/NADPH oxidase pathway via modulation of GPR 12 receptor signaling.
Significance: This study is the first to report that nesfatin-1 may be a potential therapeutic agent for nephrocalcinosis/nephrolithiasis via modulation of GPR12 receptor signaling pathway. This study also highlights nesfatin-1's protective role against kidney stone formation and related tubular injury by suppressing the oxidative PKCα/NADPH oxidase pathway.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Arti Dhar reports financial support was provided by ICMR, Govt. of India. Dr. Arti Dhar reports a relationship with BITS Pilani - Hyderabad Campus that includes: employment. Dr. Arti Dhar has patent Not applicable pending to None. The authors have declared that there is no conflict of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Calcium oxalate; GRP 12; Nephrolithiasis; Nesfatin-1; Oxidative stress; PKCα/NADPH oxidase
Substance Nomenclature: 0 (Nucleobindins)
EC 1.6.3.- (NADPH Oxidases)
EC 2.7.11.13 (Protein Kinase C-alpha)
0 (Receptors, G-Protein-Coupled)
0 (Nucb2 protein, mouse)
2612HC57YE (Calcium Oxalate)
SCR Disease Name: Nephrolithiasis, Calcium Oxalate
Entry Date(s): Date Created: 20260623 Date Completed: 20260811 Latest Revision: 20260811
Update Code: 20260812
DOI: 10.1016/j.lfs.2026.124544
PMID: 42335987
Βάση Δεδομένων: MEDLINE
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  Data: Nesfatin-1 mitigates calcium oxalate nephropathy in mice through GPR12 receptor modulation and PKCα/NADPH oxidase pathway inhibition.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Lahane+GP%22&quot;&gt;Lahane GP&lt;/searchLink&gt;; Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Bhat+A%22&quot;&gt;Bhat A&lt;/searchLink&gt;; Department of Life Science, Central University of Karnataka, Kalaburagi, 585367, India.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Kulkarni+O%22&quot;&gt;Kulkarni O&lt;/searchLink&gt;; Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Dhar+A%22&quot;&gt;Dhar A&lt;/searchLink&gt;; Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India. Electronic address: artidhar@hyderabad.bits-pilani.ac.in.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Aims: Nephrolithiasis, a prevalent and recurring kidney disease is associated with oxidative stress, inflammation, apoptosis, necroptosis, and fibrosis. Nesfatin-1, a bioactive peptide, is known to have antioxidant, anti-inflammatory, and antifibrotic properties, however, its role in nephrolithiasis associated pathological changes remains unexplored. Moreover, the receptor by which nesfatin-1 exerts its protective effects is unknown. Thus, the present study aimed to elucidate the role and underlying molecular mechanisms of nesfatin-1 in a mouse model of glyoxylate-induced nephrolithiasis/nephrocalcinosis.&lt;br /&gt;Materials and Methods: Mouse model of nephrolithiasis was created via administration of glyoxylate, and cell injury models of tubular epithelial cells were done using calcium oxalate monohydrate (COM). Kidney function, histopathology, oxidative stress, inflammation, apoptosis, and renal interstitial fibrosis were measured using assay kits, confocal microscopy and protein/mRNA expression analysis. Moreover, co-immunoprecipitation was performed to investigate the receptors involved and underlying molecular mechanism.&lt;br /&gt;Key Findings: Nephrolithiasis mice showed reduced nesfatin-1 expression and elevated markers of kidney damage, including, histological abnormalities, inflammation, necroptosis, and fibrosis. Mechanistically, nesfatin-1 modulated the GPR 12 oligomerization and inhibited the COM-induced PKCα/NADPH oxidase pathway via modulation of GPR 12 receptor signaling.&lt;br /&gt;Significance: This study is the first to report that nesfatin-1 may be a potential therapeutic agent for nephrocalcinosis/nephrolithiasis via modulation of GPR12 receptor signaling pathway. This study also highlights nesfatin-1&#39;s protective role against kidney stone formation and related tubular injury by suppressing the oxidative PKCα/NADPH oxidase pathway.&lt;br /&gt; (Copyright &#169; 2026 Elsevier Inc. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Arti Dhar reports financial support was provided by ICMR, Govt. of India. Dr. Arti Dhar reports a relationship with BITS Pilani - Hyderabad Campus that includes: employment. Dr. Arti Dhar has patent Not applicable pending to None. The authors have declared that there is no conflict of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
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  Data: &lt;i&gt;Keywords: &lt;/i&gt;Calcium oxalate; GRP 12; Nephrolithiasis; Nesfatin-1; Oxidative stress; PKCα/NADPH oxidase
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  Data: Nephrolithiasis, Calcium Oxalate
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        Text: English
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        Type: general
      – SubjectFull: Signal Transduction drug effects
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      – TitleFull: Nesfatin-1 mitigates calcium oxalate nephropathy in mice through GPR12 receptor modulation and PKCα/NADPH oxidase pathway inhibition.
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