Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 53 min ago
Peer-reviewedCC BY-NC-ND 4.0In Vivo

Impact of SPAK Deficiency on Glomerular Injury and Mitochondrial Homeostasis in Adriamycin-Induced FSGS

  • CHIEN-WEI HUANG1,2
  • HSIN-HUNG CHEN3
  • JIN-SHUEN CHEN1,4
4 affiliations
  1. 1Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
  2. 2School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C.
  3. 3Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
  4. 4Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan, R.O.C.
Read full textPDFDOICite

Abstract

Background/Aim: Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury, mitochondrial dysfunction, oxidative stress, and metabolic remodeling. STE20/SPS1-related proline-alanine-rich kinase (SPAK), a downstream component of WNK signaling, regulates renal ion transport and has been implicated in inflammatory and stress responses. This study examined the impact of SPAK deficiency on renal injury and mitochondrial homeostasis in Adriamycin-induced FSGS.

Materials and Methods: Eight-week-old male wild-type and global SPAK knockout C57BL/6 mice received a single intravenous injection of Adriamycin (18 mg/kg) or saline and were followed for four weeks. Renal function, proteinuria, glomerular histology, podocyte markers, mitochondrial dynamics, oxidative stress, apoptosis, and targeted metabolic profiles were assessed using biochemical assays, histology, immunohistochemistry, TUNEL staining, western blotting, quantitative PCR, and LC-MS-based metabolomics.

Results: Adriamycin induced proteinuria, serum creatinine elevation, glomerulosclerosis, and reduced nephrin and podocin expression in both wild-type and SPAK knockout mice. The severity of renal functional and histological injury was comparable between the two FSGS groups. SPAK deficiency was associated with baseline mitochondrial and apoptotic abnormalities, including reduced ATP5A1 expression and increased TUNEL-positive cells. In FSGS kidneys, SPAK deficiency did not restore ATP5A1, OPA1, PGC-1α, redox balance, or glycolytic remodeling, and SPAK-knockout FSGS mice exhibited greater apoptosis than wild-type FSGS mice.

Conclusion: SPAK deficiency modifies mitochondrial and apoptotic responses but does not attenuate Adriamycin-induced glomerular injury. These findings suggest that SPAK contributes to glomerular homeostasis and that its role in kidney injury is context-dependent.

Related

  1. Erbin deficiency exacerbates sepsis-induced liver injury through mitochondrial ROS/NLRP3-mediated inflammatory responses
    Jing Zuo, Xing Wang, Guoqing Jing +2
    Molecular Medicine ReportsPeer-reviewedCC BY-NC-ND 4.0Full textEpidemiology & public healthPMC
  2. Adipocyte-specific mitochondrial intermediate peptidase (Mipep) deficiency protects against LPS-induced lethal inflammation through GDF15- and FGF21-independent mechanisms
    Tomoyoshi Fukuoh, Yuka Nozaki, Kota Nagasawa +8
    Scientific ReportsPeer-reviewedCC BY 4.0Full textEpidemiology & public healthCrossref
  3. Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension with HADHA-associated improvements in fatty acid oxidation and mitochondrial redox homeostasis
    Xinyu Bai, Keke Tian, Shiyuan Song +6
    Redox BiologyPeer-reviewedCC BYFull textMolecular biology & gene regulationGeneral biologyDOAJ
  4. Niosomal Mexiletine Attenuates Rotenone-Induced Parkinsonism via Modulation of the circDLGAP4/miR-134-5p/p-CREB Axis and Restoration of Mitochondrial-Autophagic Homeostasis.
    Eman M Raafat, Fares Farhan Alanazi, Sarah Khalifah Alanazi +3
    Pharmaceuticals (Basel, Switzerland)Peer-reviewedCC BYFull textNeurologyEurope PMC
  5. Nintedanib-induced Glomerular Microangiopathy after Long-term Nintedanib Administration Presenting with Nephrotic Syndrome
    Mizuki Watada, Yurina Yataka, Motoki Hoshino +4
    Internal MedicinePeer-reviewedCC BY-NC-NDFull textGeneral medicineJ-STAGE

Cite

BibTeXRIS
BibTeX
@article{huang2026impact,
  title = {{Impact of SPAK Deficiency on Glomerular Injury and Mitochondrial Homeostasis in Adriamycin-Induced FSGS}},
  author = {CHIEN-WEI HUANG and HSIN-HUNG CHEN and JIN-SHUEN CHEN},
  journal = {In Vivo},
  year = {2026},
  month = oct,
  doi = {10.21873/invivo.14492},
  url = {https://doi.org/10.21873/invivo.14492},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Impact of SPAK Deficiency on Glomerular Injury and Mitochondrial Homeostasis in Adriamycin-Induced FSGS
AU  - CHIEN-WEI HUANG
AU  - HSIN-HUNG CHEN
AU  - JIN-SHUEN CHEN
PY  - 2026
DA  - 2026/10/29
JO  - In Vivo
DO  - 10.21873/invivo.14492
UR  - https://doi.org/10.21873/invivo.14492
AB  - Background/Aim: Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury, mitochondrial dysfunction, oxidative stress, and metabolic remodeling. STE20/SPS1-related proline-alanine-rich kinase (SPAK), a downstream component of WNK signaling, regulates renal ion transport and has been implicated in inflammatory and stress responses. This study examined the impact of SPAK deficiency on renal injury and mitochondrial homeostasis in Adriamycin-induced FSGS.  Materials and Methods: Eight-week-old male wild-type and global SPAK knockout C57BL/6 mice received a single intravenous injection of Adriamycin (18 mg/kg) or saline and were followed for four weeks. Renal function, proteinuria, glomerular histology, podocyte markers, mitochondrial dynamics, oxidative stress, apoptosis, and targeted metabolic profiles were assessed using biochemical assays, histology, immunohistochemistry, TUNEL staining, western blotting, quantitative PCR, and LC-MS-based metabolomics.  Results: Adriamycin induced proteinuria, serum creatinine elevation, glomerulosclerosis, and reduced nephrin and podocin expression in both wild-type and SPAK knockout mice. The severity of renal functional and histological injury was comparable between the two FSGS groups. SPAK deficiency was associated with baseline mitochondrial and apoptotic abnormalities, including reduced ATP5A1 expression and increased TUNEL-positive cells. In FSGS kidneys, SPAK deficiency did not restore ATP5A1, OPA1, PGC-1α, redox balance, or glycolytic remodeling, and SPAK-knockout FSGS mice exhibited greater apoptosis than wild-type FSGS mice.  Conclusion: SPAK deficiency modifies mitochondrial and apoptotic responses but does not attenuate Adriamycin-induced glomerular injury. These findings suggest that SPAK contributes to glomerular homeostasis and that its role in kidney injury is context-dependent.
SN  - 0258-851X
SN  - 1791-7549
ER  -