FKBP12 was identified as a binding protein of tacrolimus (Tac). Tac binds to FKBP12 and exhibits immunosuppressive effects in T cells. Although it is reported that Tac treatment directly ameliorates the dysfunction of the podocyte in nephrotic syndrome, the precise pharmacological mechanism of Tac is not well understood yet. It is also known that FKBP12 functions independently of Tac. However, the localization and the physiological function of FKBP12 are not well elucidated. In this study, we observed that FKBP12 is highly expressed in glomeruli, and the FKBP12 in glomeruli is restricted in podocytes. FKBP12 in cultured podocytes was expressed along the actin cytoskeleton and associated with filamentous actin (F-actin). FKBP12 interacted with the actin-associated proteins 14-3-3 and synaptopodin. RNA silencing for FKBP12 reduced 14-3-3 expression, F-actin staining, and process formation in cultured podocytes. FKBP12 expression was decreased in the nephrotic model caused by adriamycin (ADR) and the cultured podocyte treated with ADR. The process formation was deteriorated in the podocytes treated with ADR. Tac treatment ameliorated these decreases. Tac treatment to the normal cells increased the expression of FKBP12 at F-actin in processes and enhanced process formation. Tac enhanced the interaction of FKBP12 with synaptopodin. These observations suggested that FKBP12 at actin cytoskeleton participates in the maintenance of processes, and Tac treatment ameliorates podocyte injury by restoring FKBP12 at actin cytoskeleton.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1096/fj.202101052R | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Navigating the Collective: Nanoparticle-Assisted Identification of Leader Cancer Cells During Migration.
Life (Basel)
January 2025
The Laboratory of Personalized Chemo-Radiation Therapy, Institute of Future Biophysics, Moscow 141700, Russia.
Cancer-related deaths primarily occur due to metastasis, a process involving the migration and invasion of cancer cells. In most solid tumors, metastasis occurs through collective cell migration (CCM), guided by "cellular leaders". These leader cells generate forces through actomyosin-mediated protrusion and contractility.
View Article and Find Full Text PDFInvestigating the Pulmonary Host Response of Infection-Associated Pneumonia by Metagenomic Next-Generation Sequencing.
Biomedicines
January 2025
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
For investigating the host response in associated pneumonia, we analyzed the host genetic sequences obtained from metagenomic next-generation sequencing (mNGS). The samples for mNGS were bronchoalveolar lavage fluid (BALF) collected from the lungs of patients infected with and from patients without bacterial infections. BALF samples from patients with pneumonia were collected from the lungs of patients infected with with New Delhi metallo-β-lactamase (NDM, before treatment), A.
View Article and Find Full Text PDFNerve Enlargement in Patients with INF2 Variants Causing Peripheral Neuropathy and Focal Segmental Glomerulosclerosis.
Biomedicines
January 2025
Second Department of Internal Medicine, Division of Nephrology, Kansai Medical University, Hirakata 573-1010, Japan.
: Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuropathy primarily involving motor and sensory neurons. Mutations in INF2, an actin assembly factor, cause two diseases: peripheral neuropathy CMT-DIE (MIM614455) and/or focal segmental glomerulosclerosis (FSGS). These two phenotypes arise from the progressive degeneration affecting podocytes and Schwann cells.
View Article and Find Full Text PDFMolecular Mechanisms Underlying Substance Transport, Signal Transduction, and Anti-Stress Regulation, as Well as Anti-Alkaline Regulation via in the Cerebral Ganglion of Chinese Mitten Crab Under Alkaline Stress.
Biology (Basel)
January 2025
Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Ministry of Agriculture and Rural Affairs, Wuxi 214081, China.
(1) Background: Global climate change is intensifying, and the vigorous development and utilization of saline-alkali land is of great significance. As an important economic aquatic species in the context of saline-alkali aquaculture, it is highly significant to explore the regulatory mechanisms of under alkaline conditions. In particular, the brain (cerebral ganglion for crustaceans) serves as a vital regulatory organ in response to environmental stress; (2) Methods: In this study, a comparative transcriptome approach was employed to investigate the key regulatory genes and molecular regulatory mechanisms in the cerebral ganglion of under alkaline stress.
View Article and Find Full Text PDFHeterogeneous focal adhesion cytoskeleton nanoarchitectures from microengineered interfacial curvature to oversee nuclear remodeling and mechanotransduction of mesenchymal stem cells.
Cell Mol Biol Lett
January 2025
School of Medicine, Shanghai University, Shanghai, 200444, China.
Background: Interfacial heterogeneity is widely explored to reveal molecular mechanisms of force-mediated pathways due to biased tension. However, the influence of cell density,, curvature, and interfacial heterogeneity on underlying pathways of mechanotransduction is obscure.
Methods: Polydimethylsiloxane (PDMS)-based stencils were micropatterned to prepare the micropores for cell culture.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!