ArticleJournal of diabetes research2026
Diosmetin Restores Endoplasmic Reticulum Homeostasis to Ameliorate Podocyte Injury in Diabetic Kidney Disease by Targeting DNAJC3.
Article in Journal of diabetes research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundDiabetic kidney disease (DKD) causes high mortality and imposes a substantial healthcare burden, representing a major global public health challenge. The natural flavonoid diosmetin (DIO) shows promising therapeutic effects in DKD; however, its molecular mechanisms remain unclear. This study is aimed at clarifying the specific mechanisms and molecular targets through which DIO exerts its effects in DKD.
methodsWe established an in vitro podocyte injury model using high glucose (HG) and palmitic acid (PA) to evaluate the effects of DIO on podocyte viability. We performed transcriptomic analysis to identify potential mechanisms underlying the protective effects of DIO on podocytes, and we validated key pathway-related proteins by Western blot. We applied molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) to identify potential target proteins, and we further validated these targets using shRNA technology. Finally, we established a DKD mouse model by combining a high-fat/high-sugar diet with streptozotocin (STZ) administration to assess the therapeutic effects of DIO and its capacity to alleviate endoplasmic reticulum stress (ERS).
resultsDIO significantly attenuated HG/PA-induced podocyte injury and restored podocyte viability. Gene set enrichment analysis (GSEA) showed that the MISFOLDED_PROTEIN_BINDING pathway, which is closely associated with ERS regulation, was upregulated after DIO treatment. At the molecular level, DIO increased the expression of DNAJC3, a key regulator of endoplasmic reticulum homeostasis within this pathway, and reduced the levels of ERS-related proteins, including GRP78, P-eIF2α/eIF2α, ATF4, and CHOP. Molecular interaction analyses demonstrated that DIO has a strong binding affinity for DNAJC3, indicating a direct targeting effect. Knockdown of DNAJC3 markedly weakened the protective effects of DIO on podocytes. In vivo, DIO treatment significantly improved hyperglycemia, proteinuria, renal pathological injury, and oxidative stress in DKD mice. Notably, DIO also enhanced DNAJC3 expression and suppressed ERS in DKD mice.
conclusionsThis study clarifies the molecular basis of DIO-mediated protection in DKD, particularly in podocytes, by identifying DNAJC3 as a potential target that DIO inhibits ERS, restores ER homeostasis, and alleviates podocyte injury.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.