Background: Diabetic nephropathy (DN) is a serious complication in diabetic patients and has been considered as the main cause of end-stage renal disease. However, there are no studies on the role of stromal interaction molecule (STIM) and its two subtypes, STIM1 and STIM2, in the epithelial-to-mesenchymal transition (EMT) of podocytes induced by diabetic kidney disease (DKD). The present study suggests for the first time that STIM inhibition decreases DKD-induced EMT.

Methods: All DKD patients were diagnosed based on renal biopsies carried out at the Department of Nephrology, Zhejiang Provincial People's Hospital and selected using the Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN. Images were taken and the number of positive puncta in cells was analyzed using software equipped for immunofluorescence microscopy. STIM1, STIM2, FcγRIIa, FcγRIIb, Nephrin, CTGF, and α-SMA protein levels were detected by Western blotting analysis using the corresponding antibodies. The viability of cells was measured using CCK-8 assays. Absorbance at 450 nm was measured with a Multiskan FC Microplate Reader (Thermo Scientific, USA) and the results were normalized to those of untreated cells. All statistical analyses were performed using SPSS 19.0 software (Stanford University, Stanford, CA, USA).

Results: A total of 30 DKD patients and 30 control patients were enrolled in the study. We found that the level of urine protein in patients and db/db diabetic mice is higher than control group and the levels of STIM1 and 2 significantly increased in DKD groups. We also demonstrated that STIM is upregulated during DKD injury. Next, we discovered that DKD-induced podocyte EMT is related to STIM overexpression in vivo and in vitro. Further research demonstrated that STIM siRNA reverses podocytes from DKD-induced injury and EMT and reverses FcγRII activity in HG-treated podocytes.

Conclusion: Our study suggests that STIM and FcγRII play an essential role in the regulation of DKD-induced podocyte EMT. STIM is an essential component of FcγR activation and inhibition of STIM-mediated signaling pathway might be a new strategy to treat IgG-dependent renal diseases.

Download full-text PDF

Source
http://dx.doi.org/10.14670/HH-18-068DOI Listing

Publication Analysis

Top Keywords

stim
8
fcγrii activity
8
diabetic nephropathy
8
stim1 stim2
8
study suggests
8
dkd patients
8
demonstrated stim
8
dkd-induced podocyte
8
podocyte emt
8
emt stim
8

Similar Publications

Roles of calcium in ameloblasts during tooth development: A scoping review.

J Taibah Univ Med Sci

February 2025

Department of Prosthodontics/Dental Material, Dr. Ziauddin Ahmad Dental College, Aligarh Muslim University, India.

Objectives: Calcium ions (Ca) play crucial role in tooth development, particularly in maintaining enamel density during amelogenesis. Ameloblasts require specific proteins such as amelogenin, ameloblastin, enamelin, kallikrein, and collagen for enamel growth. Recent research has highlighted the importance of calcium and fluoride ions, as well as the TRPM7, STIM, and SOCE pathways, in regulating various stages of enamel formation.

View Article and Find Full Text PDF

Hippocampal dendritic spines store-operated calcium entry and endoplasmic reticulum content is dynamic microtubule dependent.

Sci Rep

January 2025

Laboratory of Biomedical Imaging and Data Analysis, Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, Khlopina St. 11, St. Petersburg, Russia, 194021.

One of the mechanisms of calcium signalling in neurons is store-operated calcium entry (SOCE), which is activated when the calcium concentration in the smooth endoplasmic reticulum (ER) decreases and its protein-calcium sensor STIM (stromal interacting molecule) relocate to the endoplasmic reticulum and plasma membrane junctions, forms clusters and induces calcium entry. In electrically non-excitable cells, STIM1 is coupled with the positive end of a tubulin microtubule through interaction with EB1 (end-binding) protein, which controls its oligomerization, SOCE and participates in ER movement. STIM2 homologue, which is specific for mature hippocampal dendritic spines, is known to interact with EB3 protein, however, not much is known about the role of this interaction in STIM2 clustering or ER trafficking in neurons.

View Article and Find Full Text PDF

One of the most remarkable achievements of the TKI era has been the capacity to induce deep molecular remissions that are sustainable off therapy in chronic myeloid leukemia (CML) patients - treatment-free remission (TFR). TFR was first described in a handful of patients within 3-4 years of imatinib approval. In 2004 TFR was tested in a small French pilot study, followed soon after by the French STIM and Australasian TWISTER studies.

View Article and Find Full Text PDF

Channels, Transporters, and Receptors at Membrane Contact Sites.

Contact (Thousand Oaks)

December 2024

Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.

Membrane contact sites (MCSs) are specialized regions where two or more organelle membranes come into close apposition, typically separated by only 10-30 nm, while remaining distinct and unfused. These sites play crucial roles in cellular homeostasis, signaling, and metabolism. This review focuses on ion channels, transporters, and receptors localized to MCSs, with particular emphasis on those associated with the plasma membrane and endoplasmic reticulum (ER).

View Article and Find Full Text PDF

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!