The balance between SUMOylation and deSUMOylation critically regulate cellular apoptosis, with SUMO-modified proteins implicated in ischemia/hypoxia injury. However, the specific contributions of SUMO-conjugated proteins in renal ischemia-reperfusion injury (IRI) remain poorly defined. SUMOylation in IRI was investigated Using proximal tubular-specific Senp3 conditional knockout (CKO) mice. While SENP3-deficiency did not induce tubular injury under basal conditions, its significantly attenuated renal damage following IRI. SUMOylation conferred protection against apoptosis in renal tubular epithelia cells during ischemia/hypoxia. Mass spectrometry revealed arginosuccinate synthase 1 (ASS1) as a key SUMO2/3 target (modified at K239 and K310) in IRI progression. Mechanistically, SENP3-mediated deSUMOylation promoted ASS1 nuclear accumulation in post-IRI tubular epithelial cells, subsequently activating the intrinsic apoptosis pathway via p53-dependent transcriptional upregulation. These findings nominate the SENP3-ASS1-p53 axis as a potential therapeutic target for renal IRI.

Novel coumarin derivative SZC-6 as an allosteric activator of SIRT3 alleviates diabetic kidney disease via the SIRT3-Foxo3a signaling axis.

Significance of urinary and serum neutrophil gelatinase-associated Lipocalin in Antineutrophil cytoplasmic antibody-associated Vasculitis with glomerulonephritis.

Emp3 promotes the progression of renal fibrosis in mice with unilateral ureteral obstruction by activating TGF-β/Smad3 signaling pathway.

GPR108 deficiency promotes urate-induced renal interstitial fibrosis.

Synthesis of 1,8-cineole derivatives and evaluation of their cytoprotective effects against cisplatin-induced HK-2 cell injury.

MDA5 is an innate pattern recognition receptor that is involved in the recognition of various viruses. It can recognize RNA viruses, activate downstream signalling pathways, facilitate the transcription of inflammatory factors, and induce cell pyroptosis. Pyroptosis is a form of programmed cell death accompanied by the release of inflammatory factors and an inflammatory response. In this study, we hypothesize that pyroptosis is elicited by the signalling cascade subsequent to the recognition of nephropathogenic infectious bronchitis virus (NIBV) by MDA5. Thus, we infected chicken renal tubular epithelial cells with NIBV and discovered that NIBV infection induced pyroptosis and increased the mRNA levels of MDA5. Consequently, we infected primary chicken renal tubular epithelial cells with NIBV and inhibited TRAF6 expression using the exogenous inhibitor C25-140. We found that NIBV could increase lactate dehydrogenase (LDH) levels, increase the proportion of pyroptotic cells, and increase the mRNA and protein levels of the MDA5/NF-κB signalling pathway and the classical pyroptosis pathway. Here, we selected the ubiquitin ligase TRAF6, a key node in the MDA5/NF-κB signalling pathway, from molecular biological and genetic perspectives to explore the molecular mechanism of NIBV-induced pyroptosis. After the inhibitor C25-140 was used, NIBV-induced apoptosis and the activity of the MDA5/NF-κB/NLRP3 pathway were reversed. In addition, the amount of NIBV replication in the cells was reduced. In conclusion, the MDA5/NF-κB/NLRP3 signalling pathway is involved in the regulation of pyroptosis in a NIBV-infected chicken renal tubular epithelial cell model. The inhibition of this signalling pathway can alleviate NIBV-induced pyroptosis and reduce the replication of NIBV in cells, which could become one strategy for treating NIBV.

Dual ice crystal growth strategy-enabled fabrication of interconnected-porous GelMA microcarriers for Stemness enhancement and cellular characteristic preservation.

Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is associated with increased morbidity and mortality. The pathogenesis of LN involves complex immune-mediated mechanisms that alter the biology of renal resident epithelial cells. Emerging evidence highlights the bidirectional interactions between immune cells and renal epithelial cells—including podocytes and tubular epithelial cells(TECs)—as critical contributors to disease progression. These interactions shape local immune responses, drive inflammatory injury, and disrupt renal function. However, the molecular and cellular basis of this crosstalk remains incompletely understood. Recent advances have uncovered key mechanisms underlying these interactions and identified potential therapeutic targets that may inform future treatment strategies. This review summarizes current findings on the immunological roles of renal epithelial cells in LN and discusses their relevance to the development of targeted and cell-specific therapeutic interventions.

Background Outer membrane vesicles (OMVs) secreted by enterohemorrhagic Escherichia coli (EHEC) O157 contain Shiga toxin 2 (Stx2), the major virulence factor involved in the pathogenesis of EHEC-associated hemolytic uremic syndrome (EHEC-HUS). However, it remains unclear whether EHEC OMVs produced in the human intestine during infection play a role in EHEC-HUS development. Using a mouse model, we investigated whether EHEC O157 OMVs administered by oral gavage translocate from the gastrointestinal tract to the bloodstream, enter the kidneys, and induce signs of EHEC-HUS. Because mice, unlike humans, express the Stx2 receptor Gb3 on the renal tubular epithelium but not on the glomerular endothelium, we focused on the ability of EHEC O157 OMVs to cause tubular damage, which represents a mechanism that, alongside glomerular thrombotic microangiopathy (TMA), contributes to acute kidney failure in EHEC-HUS. Methods The sera and kidneys of BALB/c mice orally administered EHEC O157 OMVs were examined for OMVs by immunoelectron and confocal immunofluorescence microscopy. Histopathological evaluation of the kidneys was performed by light and electron microscopy, and blood analyses were conducted using standard methods. The cytotoxicity of EHEC O157 OMVs toward human renal glomerular endothelial cells (HRGECs) and tubular epithelial cells (HK-2) was determined by Cell Death ELISA. In addition, sera from patients with EHEC O157-associated HUS were examined for O157 OMVs by immunoelectron microscopy. Results EHEC O157 OMVs were detected in the sera and kidneys of mice orally administered 100–400 µg of OMVs. The mice exhibited renal tubular epithelial damage and had significantly increased serum creatinine and blood urea nitrogen levels, indicating acute kidney failure. EHEC O157 OMVs induced apoptosis in HRGECs and HK-2 cells, the primary targets in EHEC-HUS. Moreover, EHEC O157 OMVs were found in the sera of patients with EHEC O157-associated HUS. Conclusion Orally administered EHEC O157 OMVs translocated from the gastrointestinal tract to the kidneys, where they caused tubular epithelial injury followed by acute kidney failure. Combined with their cytotoxicity toward HRGECs and HK-2 cells and detection in patient sera, these findings indicate that EHEC O157 OMVs contribute to the pathogenesis of EHEC-HUS.

Hypoxia-responsive modules via tunable hydrophobicity reversal enhance renal-targeted release of CD36-interfering nanoparticles to ameliorate acute kidney injury.

Actin cytoskeleton stabilization inhibits NLRP3 inflammasome activation and mitigates renal inflammation and fibrosis in obstructive nephropathy.

Rationale:Birt–Hogg–Dube (BHD) syndrome is a rare autosomal dominant disorder characterized by a triad of manifestations, including recurrent spontaneous pneumothorax, multiple cutaneous fibrofolliculomas, and renal neoplasms. Familial clustering of spontaneous pneumothorax should raise clinical suspicion of BHD syndrome. This syndrome is caused by pathogenic variants of the folliculin gene (FLCN gene) encoding folliculin, which predisposes to pneumothorax through dysregulated matrix metalloproteinase activity, leading to elastic fiber degradation in the pulmonary parenchyma.Patient concerns:A 28-year-old female presented with recurrent pneumothorax and a family history of primary spontaneous pneumothorax. Emergency video-assisted thoracoscopic surgery with bullectomy and cyst resection was performed.Diagnoses:The FLCN gene mutation was confirmed by genetic testing after surgery. The clinicopathological characteristics, molecular genetics, and therapeutic strategies for BHD syndrome have been discussed in the literature. The female who experienced 3 episodes of spontaneous pneumothorax within 24 months. Notably, her multigenerational family history included her paternal uncle and cousins affected by primary spontaneous pneumothorax.Interventions:Emergency video-assisted thoracoscopic surgery revealed multiple subpleural cysts (3–15 mm in diameter), predominantly in the lower lung lobes, requiring bullectomy and cyst wall resection. Histopathological analysis revealed characteristic thin-walled cysts lined with alveolar epithelium. Postoperative genetic sequencing revealed a heterozygous splice-site variant in FLCN gene, establishing a diagnosis of BHD syndrome.Outcomes:After regular follow-up, the patient had no recurrence of spontaneous pneumothorax, such as bullae rupture, until recently. This case highlights the importance of integrating radiological findings with molecular diagnostics for the evaluation of recurrent pneumothorax. It is particularly necessary to emphasize that the patient and her legal guardian has given us informed consent. Chengdu-Shangjin Nanfu Hospital ethics Committee has approved this study.Lessons:This case shows a typical phenomenon of family clustering that should raise clinical suspicion of BHD syndrome. BHD syndrome is a rare autosomal dominant genetic disorder that caused by mutations in FLCN gene. The gene is a tumor suppressor gene that encodes the follicle-stimulating hormone folliculin. Follicle-stimulating hormone folliculin is expressed in most tissues, including the skin and its appendages, type I alveolar epithelial cells, and distal renal tubular epithelial cells, which explains why BHD syndrome occurs in the skin, lungs, and kidneys. The literature review shows that there are 12 similar cases, including the male-to-female ratio and average age. Thoracoscopic surgery had the best effect, followed by conservative treatment, and the recurrence rate was higher after closed thoracic drainage. Due to the rarity of this syndrome, this article reminds clinicians to pay attention to its familial clustering characteristics during diagnosis and treatment, and also reminds other family members to pay attention to screening for the clinical features related to this syndrome, so as to facilitate early treatment. Furthermore, this case also provides significant reference value for identifying the causes and molecular mechanisms of spontaneous pneumothorax, especially those with a familial clustering tendency.

Various autoimmune diseases frequently cause both acute and chronic kidney injuries through complex mechanisms involving autoantibodies and cellular immune responses that result in tissue damage. Intercalated cells (ICs), specialized renal tubular epithelial cells responsible for proton secretion, are strategically positioned at the epithelial-immune interface, making them ideal sensors of stress signals and potential triggers of immune responses. This study investigates the molecular mechanisms by which ICs interact with immune cells to maintain renal immune homeostasis and contribute to the development of autoimmune kidney disease. We depleted Foxp3⁺ regulatory T cells (Tregs) by injecting diphtheria toxin (DT) into male and female Foxp3-DTR mice. Two weeks after depletion, we observed autoimmune inflammation marked by increased renal immune infiltration, including neutrophils, macrophages, and subsets of T and B cells, along with the formation of ectopic lymphoid-like structures and enhanced antigen presentation. We found higher levels of renal autoantibodies in urine and serum, with antibodies depositing in glomeruli and tubules. Our analysis identified several renal antigens targeted by autoantibodies, suggesting their potential role in antibody-mediated renal injury. Kidney damage included smaller glomeruli, proximal tubular injury, an increased urine albumin/creatinine ratio, and decreased urine output. Disruption of immune tolerance led to the upregulation of inflammasome-related genes and IL-33 in ICs, which acts as a key alarmin signaling damage and promoting activation and expansion of Tregs. Our findings uncover a novel IC-Treg interaction mediated by the IL-33 pathway, revealing immune-regulating mechanisms that support renal immune tolerance. Although Tregs were initially depleted, a significant rebound in their numbers and function occurred. Understanding the cellular and molecular mechanisms behind autoimmune renal injury is crucial for developing targeted therapies and identifying appropriate biomarkers.

Molecular mechanisms and targeted intervention strategies of renal tubular epithelial cell glycolytic reprogramming in renal fibrosis.

Sepsis-associated acute kidney injury (S-AKI) is a critical condition characterized by renal tubular epithelial cell apoptosis and abnormal cytoskeleton. This study aims to investigate the role of the m6A modification-dependent protein HNRNPC in regulating renal cell apoptosis and cytoskeleton in S-AKI. Dot blot analysis was employed to assess the total m6A levels. Cell viability, flow cytometry, and fluorescent phalloidin staining were used to evaluate the role of HNRNPC in CD80-dependent apoptosis and cytoskeletal remodeling. RNA sequencing and subsequent data analysis highlighted the involvement of the NF-κB signaling pathway. Luciferase reporter assays and Western blot were used to establish that HNRNPC transcriptionally promotes CD80 expression. Bioinformatics, EMSA, and ChIP assays further confirmed the role of NF-κB in regulating CD80. Additionally, MeRIP-qPCR and RNA m6A quantification demonstrated that HNRNPC facilitates apoptosis through m6A-dependent regulation of NF-κB. Induction of HNRNPC to a higher level can induce apoptosis and cytoskeletal deformation in renal tubular cells. Meanwhile, CD80 was essential for HNRNPC-induced tubular injury. Further experiments showed that HNRNPC regulated NF-κB mRNA dependent on m6A modification. Moreover, NF-κB acted as a transcription factor to promote CD80 expression. In vivo experiments further verified the relationships between HNRNPC, NF-κB, and CD80 and demonstrated the significance of HNRNPC in CD80-associated apoptosis. This study elucidates the molecular mechanisms underlying the pathogenesis of S-AKI and highlights the potential of HNRNPC and CD80 as therapeutic targets to reduce renal damage in S-AKI.

Pathological feature in chronic myeloid leukemia patients with proteinuria receiving olverembatinib therapy

The progression of renal fibrosis is difficult to reverse, and Poria cocos, one of the main components of Wenyang Zhenshuai Granules, has been shown to be crucial to the development of the epithelial-mesenchymal transition (EMT). This study aimed to examine the molecular mechanism by which Poricoic Acid A (PAA) inhibited the advancement of EMT in renal tubular epithelial (RTE) cells. The protein levels of sprouty RTK signaling antagonist 2 (SPRY2) extracellular regulated protein kinases (ERK), and p-ERK were measured. The EMT progression of RTE cells was evaluated by a series of experiments. The regulatory relationship of PAA to SPRY2 was determined by cycloheximide, molecular docking and drug affinity target stability and immunoprecipitation. The overexpression of SPRY2 or PAA intervention suppressed the HK-2 and NRK-52E cell's viability, proliferation and migration ability of TGF-β1-induced while raising the levels of E-cadherin and decreasing those of collagen I, collagen III, Fibronectin1, α-SMA, Vimentin, ZEB1, Twist, Snail and Slug. PAA was able to be combined with SPRY2 protein. Besides, we found that PAA intervention increased the stability of SPRY2 through the ubiquitin-proteasome pathway, did not affect ERK levels, and reduced the levels of p-ERK. Finally, we found that inhibiting SPRY2 negated the beneficial effect of PAA on TGF-β1-stimulated RTE cells. PAA alleviated the EMT of RTE cells by modulating the SPRY2/ERK pathway.

MicroRNA-93-5p alleviates uric acid-induced fibrosis in renal tubular epithelial cells by regulating the SMAD5/Id2 signaling pathway.

Alternative splicing as a novel pathogenic mechanism in chronic kidney disease.