In vitro SELEX and application of an African swine fever virus (ASFV) p30 protein specific aptamer.

The African swine fever virus (ASFV) has caused severe economic losses in the pig industry. To monitor ASFV spread, the p30 protein has been identified as an ideal infection marker due to its early and long-term expression during the ASFV infection period. Timely monitoring of ASFV p30 enables the detection of ASFV infection and assessment of disease progression. Aptamers are an outstanding substitute for antibodies to develop an efficient tool for ASFV p30 protein detection. In this study, a series of aptamer candidates were screened by in vitro magnetic bead-based systematic evolution of ligands by exponential enrichment (MB-SELEX). An aptamer (Atc-20) finally showed high specificity and affinity (Kd = 140 ± 10 pM) against ASFV p30 protein after truncation and affinity assessment. Furthermore, an aptamer/antibody heterogeneous sandwich detection assay was designed based on Atc20, achieving a linear detection of ASFV p30 ranging from 8 to 125 ng/ml and a detection limit (LOD) of 0.61 ng/ml. This assay showed good analytical performances and effectively detected p30 protein in diluted serum samples, presenting promising potential for the development of ASFV biosensors.

Metabolic implications of amino acid metabolites in chronic kidney disease progression: a metabolomics analysis using OPLS-DA and MBRole2.0 database.

BACKGROUND: As chronic kidney disease (CKD) progresses, metabolites undergo diverse transformations. Nevertheless, the impact of these metabolic changes on the etiology, progression, and prognosis of CKD remains uncertain. Our objective is to conduct a metabolomics analysis to scrutinize metabolites and identify significant metabolic pathways implicated in CKD progression, thereby pinpointing potential therapeutic targets for CKD management. METHODS: We recruited 145 patients with CKD and determined their mGFR by measuring the plasma iohexol clearance, whereupon we partitioned them into four groups based on their mGFR values. Non-targeted metabolomics analysis was conducted using UPLC-MS/MS assays. Differential metabolites were identified via one-way ANOVA, PCA, PLS-DA, and OPLS-DA analyses employing the MetaboAnalyst 5.0 platform. Ultimately, we performed differential metabolite pathway enrichment analysis, using both the MetaboAnalyst 5.0 platform and the MBRole2.0 database. RESULTS: According to the findings of the MBRole2.0 and MetaboAnalyst 5.0 enrichment analysis, six amino acid metabolism pathways were discovered to have significant roles in the progression of CKD, with the glycine, serine, and threonine metabolism pathway being the most prominent. The latter enriched 14 differential metabolites, of which six decreased while two increased concomitantly with renal function deterioration. CONCLUSIONS: The metabolic analysis unveiled that glycine, serine, and threonine metabolism plays a pivotal role in the progression of CKD. Specifically, glycine was found to increase while serine decreased with the deterioration of CKD.

Ultrasensitive Electrochemical Aptasensing of Malathion Based on Hydroxylated Black Phosphorus/Poly-L-Lysine Composite.

A highly sensitive unlabeled electrochemical aptasensor based on hydroxylated black phosphorus/poly-L-lysine (hBP/PLL) composite is introduced herein for the detection of malathion. Poly-L-lysine (PLL) with adhesion and coating properties adhere to the surface of the nanosheets by noncovalent interactions with underlying hydroxylated black phosphorus nanosheets (hBP) to produce the hBP/PLL composite. The as-synthesized hBP/PLL composite bonded to Au nanoparticles (Au NPs) firmly by assembling and using them as a substrate for the aptamer with high specificity as a probe to fabricate the sensor. Under optimal conditions, the linear range of the electrochemical aptasensor was 0.1 pM~1 µM, and the detection limit was 2.805 fM. The electrochemical aptasensor has great selectivity, a low detection limit, and anti-interference, which has potential application prospects in the field of rapid trace detection of pesticide residues.

Novel Metabolites to Improve Glomerular Filtration Rate Estimation.

INTRODUCTION: The glomerular filtration rate (GFR) is crucial for chronic kidney disease (CKD) diagnosis and therapy. Various studies have sought to recognize ideal endogenous markers to improve the estimated GFR for clinical practice. To screen out potential novel metabolites related to GFR (mGFR) measurement in CKD patients from the Chinese population, we identified more biomarkers for improving GFR estimation. METHODS: Fifty-three CKD participants were recruited from the Third Affiliated Hospital of Sun Yat-sen University in 2020. For each participant, mGFR was evaluated by utilizing the plasma clearance of iohexol and collecting serum samples for untargeted metabolomics analyses by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. All participants were divided into four groups according to mGFR. The metabolite peak area data were uploaded to MetaboAnalyst 5.0 for one-way analysis of variance, principal component analysis, and partial least squares-discriminant analysis and confirmed the metabolites whose levels increased or decreased with mGFR and variable importance in projection (VIP) values >1. Metabolites were ranked by correlation with the original values of mGFR, and metabolites with a correlation coefficient >0.8 and VIP >2 were identified. RESULTS: We screened out 198 metabolites that increased or decreased with mGFR decline. After ranking by correlation with mGFR, the top 50 metabolites were confirmed. Further studies confirmed the 10 most highly correlated metabolites. CONCLUSION: We screened out the metabolites that increased or decreased with mGFR decline in CKD patients from the Chinese population, and 10 of them were highly correlated. They are potential novel metabolites to improve GFR estimation.

A Metabolomics study of metabolites associated with the glomerular filtration rate.

BACKGROUND: Chronic kidney disease (CKD) is a global public health issue. The diagnosis of CKD would be considerably enhanced by discovering novel biomarkers used to determine the glomerular filtration rate (GFR). Small molecule metabolites related to kidney filtration function that might be utilized as biomarkers to measure GFR more accurately could be found via a metabolomics analysis of blood samples taken from individuals with varied glomerular filtration rates. METHODS: An untargeted metabolomics study of 145 plasma samples was performed using ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The 145 samples were divided into four groups based on the patient's measured glomerular filtration rates (mGFRs) determined by the iohexol plasma clearance rate. The data were analyzed using random forest analyses and six other unique statistical analyses. Principal component analysis (PCA) was conducted using R software. RESULTS: A large number of metabolites involved in various metabolic pathways changed significantly between groups with different GFRs. These included metabolites involved in tryptophan or pyrimidine metabolism. The top 30 metabolites that best distinguished between the four groups in a random forest plot analysis included 13 amino acids, 9 nucleotides, and 3 carbohydrates. A panel of metabolites (including hydroxyaparagine, pseudouridine, C-glycosyltryptophan, erythronate, N-acetylalanine, and 7-methylguanidine) for estimating GFR was selected for future testing in targeted analyses by combining the candidate lists with the six other statistical analyses. Both hydroxyasparagine and N,N-dimethyl-proline-proline are unique biomarkers shown to be inversely associated with kidney function that have not been reported previously. In contrast, 1,5-anhydroglucitol (1,5-AG) decreases with impaired renal function. CONCLUSIONS: This global untargeted metabolomics study of plasma samples from patients with different degrees of renal function identified potential metabolite biomarkers related to kidney filtration. These novel potential metabolites provide more insight into the underlying pathophysiologic processes that may contribute to the progression of CKD, lead to improvements in the estimation of GFR and provide potential therapeutic targets to improve kidney function.

Metabolic profiling identifies the significance of caffeine metabolism in CKD.

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear. Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment. Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC-MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression. Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine. Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

Identification of Metabolite Markers Associated with Kidney Function.

Background: Chronic kidney disease (CKD) is a global public health problem. Identifying new biomarkers that can be used to calculate the glomerular filtration rate (GFR) would greatly improve the diagnosis and understanding of CKD at the molecular level. A metabolomics study of blood samples derived from patients with widely divergent glomerular filtration rates could potentially discover small molecule metabolites associated with varying kidney function. Methods: Using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), serum was analyzed from 53 participants with a spectrum of measured GFR (by iohexol plasma clearance) ranging from normal to severe renal insufficiency. An untargeted metabolomics assay (N » 214) was conducted at the Calibra-Metabolon Joint Laboratory. Results: From a large number of metabolomics-derived metabolites, the top 30 metabolites correlated to increasing renal insufficiency according to mGFR were selected by the random forest method. Significant differences in metabolite profiles with increasing stages of CKD were observed. Combining candidate lists from six other unique statistical analyses, six novel, potential metabolites that were reproducibly strongly associated with mGFR were selected, including erythronate, gulonate, C-glycosyltryptophan, N-acetylserine, N6-carbamoylthreonyladenosine, and pseudouridine. In addition, hydroxyasparagine were strongly associated with mGFR and CKD, which were unique to this study. Conclusions: Global metabolite profiling of serum yielded potentially valuable biomarkers of different stages of CKD. Additionally, these potential biomarkers might provide insight into the underlying pathophysiologic processes that contribute to the progression of CKD as well as improve GFR estimation.

Clinical assessment of nutritional status using the modified quantified subjective global assessment and anthropometric and biochemical parameters in patients undergoing hemodialysis in Macao.

OBJECTIVE: Malnutrition is widespread among patients undergoing hemodialysis and is linked to high morbidity and mortality rates. We evaluated the nutritional status and malnutrition markers in patients undergoing hemodialysis in Macao. METHODS: We performed a cross-sectional analysis of 360 patients in a hemodialysis center. The modified quantitative subjective global assessment (MQSGA), anthropometric indices and related biochemical test data were used to evaluate nutritional status. RESULTS: The sample's mean age was 63.47 ± 13.95 years. There were 210 well-nourished (58.3%), 139 mild-to-moderately malnourished (38.6%) and 11 severely malnourished (3.1%) patients. Older patients had a higher incidence of severe malnutrition, but there were no significant differences between diabetic and non-diabetic patients. Mid-arm circumference (MAC); mid-arm muscle circumference; body mass index; triceps skin fold thickness; serum albumin, creatinine and urea; and hemoglobin were all valid for assessing nutritional status. MAC and the serum albumin and creatinine concentrations significantly negatively correlated with MQSGA. CONCLUSIONS: Malnutrition is commonplace in patients undergoing hemodialysis in Macao, but their nutritional status is not affected by diabetes. Serum creatinine, serum albumin and MAC, and especially pre-dialysis creatinine concentration, represent effective, readily available, and easily remembered screening measures of nutritional status for patients undergoing maintenance dialysis.

A two-stage neural network prediction of chronic kidney disease.

Accurate detection of chronic kidney disease (CKD) plays a pivotal role in early diagnosis and treatment. Measured glomerular filtration rate (mGFR) is considered the benchmark indicator in measuring the kidney function. However, due to the high resource cost of measuring mGFR, it is usually approximated by the estimated glomerular filtration rate, underscoring an urgent need for more precise and stable approaches. With the introduction of novel machine learning methodologies, prediction performance is shown to be significantly improved across all available data, but the performance is still limited because of the lack of models in dealing with ultra-high dimensional datasets. This study aims to provide a two-stage neural network approach for prediction of GFR and to suggest some other useful biomarkers obtained from the blood metabolites in measuring GFR. It is a composite of feature shrinkage and neural network when the number of features is much larger than the number of training samples. The results show that the proposed method outperforms the existing ones, such as convolutionneural network and direct deep neural network.

Exploring protective effect of Glycine tabacina aqueous extract against nephrotic syndrome by network pharmacology and experimental verification.

BACKGROUND: Glycine tabacina (Labill.) Benth, one of the traditional Chinese herbal medicines, has been used for treatment of nephritis, osteoporosis, rheumatism, and menopausal syndrome. The aim of this study was to illuminate the therapeutic effect and mechanism of Glycine tabacina aqueous extract (GATE) in the treatment of nephrotic syndrome (NS). METHODS: UHPLC-DAD-MS/MS was used to analyze the chemical profile of GATE. Adriamycin (ADR)-induced NS mouse model and network pharmacology methods were conducted to explore the protective effect and mechanism of GATE on NS treatment. RESULTS: GATE administration significantly ameliorated symptoms of proteinuria and hyperlipidemia in NS mice, as evidenced by reduced excretion of urine protein and albumin, and decreased plasma levels of total cholesterol and triglyceride. Decreased blood urea nitrogen (BUN) and creatinine levels in NS mice suggested that GATE could prevent renal function decline caused by ADR. GATE treatment also inhibited ADR-induced pathological lesions of renal tissues as indicated by periodic acid Schiff staining. Six flavonoids of GATE were identified by using UHPLC-DAD-MS/MS. Network pharmacology analysis indicated that the protection of GATE in treating NS might be associated with the regulation of oxidative stress and inflammation. In addition, the in vivo experiment validated that treatment with GATE markedly decreased reactive oxygen species production, malonaldehyde level, and increased superoxide dismutase activity both in plasma and renal tissues. TNF-α level in plasma and protein expression in kidney were significantly decreased in GATE treatment groups. CONCLUSIONS: Combination of network pharmacology analysis and experimental verification revealed that GATE exerts anti-NS effect possibly through modulating oxidative stress and inflammation, suggesting the potential application of GATE or its derivatives in the prevention and treatment of NS and other related kidney diseases.

Therapeutic targets for the anemia of predialysis chronic kidney disease: a meta-analysis of randomized, controlled trials.

Anemia is one of the major complications in predialysis patients with chronic kidney disease (CKD). A clearer cognition of the prognostic impact of hemoglobin (Hb) or hematocrit (Hct) target on the outcomes of predialysis patients with CKD is significant. This article aims to establish the suitable hemoglobin target to provide clinical guidance. MEDLINE, EmBase, the Cochrane Library and other databases were searched with both MeSH terms and keywords to gather researches that assessed all-cause mortality, stroke, treatment of renal replacement, and transfusion. The meta-analysis was accomplished via Revman 5.3 version. Totally, 13 eligible studies involving 7606 patients were included. There was a significantly lower risk of transfusion (risk ratio (RR) 0.59, 95% CI 0.52 to 0.67; p<0.00001) in the higher hemoglobin group than in the lower one. However, no significant difference was found in all-cause mortality (RR 1.10, 95% CI 0.98 to 1.23; p=0.11), stroke (RR 1.32, 95% CI 0.82 to 2.10; p=0.25) and treatment of renal replacement including hemodialysis, peritoneal dialysis and renal transplant (RR 1.08, 95% CI 0.95 to 1.22; p= 0.23) between the higher hemoglobin group and the lower one. The results favor the higher hemoglobin target. To target the higher hemoglobin when treating predialysis patients with CKD may decrease the risk of transfusion without increasing the risk of death, stoke, and treatment of renal replacement.

Hepatoprotective effects of raspberry (Rubus coreanus Miq.) seed oil and its major constituents.

Raspberry seed is a massive byproduct of raspberry juice and wine but usually discarded. The present study employed a microwave-assisted method for extraction of raspberry seed oil (RSO). The results revealed that omega-6 fatty acids (linoleic acid and γ-linolenic acid) were the major constituents in RSO. Cellular antioxidant enzyme activity such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were investigated in HepG2 cells treated with RSO. Induction of the synthesis of several antioxidants in H2O2-exposed HepG2 cells was found. RSO increased the enzyme activity of SOD, CAT, and GPx in H2O2-exposed HepG2. Furthermore, RSO inhibited the phosphorylation of upstream mitogen-activated protein kinases (MAPK) such as c-Jun N-terminal kinase (c-JNK) and extracellular signal-regulated kinase (ERK). Taken together, the possible mechanisms to increase antioxidant enzyme activities in HepG2 may through the suppression of ERK and JNK phosphorylation. Raspberry seed oil exhibited good effects on the activities of the intracellular antioxidant enzymes and seems to protect the liver from oxidative stress through the inhibition of MAPKs.

Inflammation but not dietary macronutrients insufficiency associated with the malnutrition-inflammation score in hemodialysis population.

Malnutrition is associated with increased risk of mortality in hemodialysis patients. And insufficient dietary intake is the common cause for malnutrition. So, in order to survey the dietary intake of hemodialysis patients and study the relationship between the dietary feature and nutritional status, a cross-sectional study was performed. 75 hemodialysis patients from South China participated in the dietary intake survey and nutrition assessment. A three-day diet diary record was used to estimate the major dietary macronutrients. Nutritional status was assessed by malnutrition-inflammation score (MIS) in addition to several related anthropometric measurements. Serum albumin, transferrin, and high-sensitivity C-reactive protein (CRP) were measured. Receiver operating characteristic (ROC) curve analysis was used to quantify the assessing value of independent parameters for nutritional status. The results showed that 48% patients were malnourished according to the MIS. The malnourished patients had a lower body mass index (BMI), fat mass (FM), albumin and a higher level of CRP, compared with normal nourished patients (P < 0.05). However, no significant differences of macronutrients (calories, protein, fat, carbohydrates, etc) were found between the two nutrition groups (P > 0.05). The multivariate regression analysis showed that the major macronutrients had no significant association with MIS (P > 0.05). In conclusion, malnutrition is very common in South China hemodialysis population and these data indicated that inflammation but not dietary macronutrients insufficiency might be the candidate cause for malnutrition in hemodialysis population.

The insufficiency intake of dietary micronutrients associated with malnutrition-inflammation score in hemodialysis population.

The relations between dietary micronutrient, nutritional status and inflammation in hemodialysis patients are still unclear. A cross-sectional study was performed in hemodialysis population. 75 hemodialysis patients from South China participated in the dietary and nutritional assessment. Clinical and dietary data were collected. Nutritional status was assessed by Malnutrition-Inflammation Score (MIS) in addition to related anthropometric measurements. And according to the MIS score, the whole hemodialysis patients were divided into normal nutrition group and malnutrition group. The results showed that mid arm circumference (MAC) negatively correlated with MIS (r = -0.425; P = 0.002). The area under the ROC curve (AUC) for MAC was 0.737 (0.614-0.859). Comparing with the normal nutritional group, lower dietary selenium (Se), copper (Cu), iodine (I) and manganese (Mn) intake were observed among patients with malnutrition (P<0.05). While no significant differences of diverse vitamins were found. In conclusion, MAC was effective indicator for assessing nutritional and inflammatory status (P<0.05). The reduction of dietary Se, Cu, I and Mn intake level may be alarming markers for malnutrition and inflammatory status in hemodialysis patients.

Combination with anthropometric measurements and MQSGA to assess nutritional status in Chinese hemodialysis population.

AIMS: To assess the nutritional status, combination with anthropometric measurements and modified quantitative subjective global assessment (MQSGA) was used in multi-center hemodialysis population in South China. METHODS: A cross-sectional, descriptive-analytic study was performed in 4 teaching hospitals in South China, dated from January 2010 to December 2011. Nutritional status was assessed with MQSGA and related anthropometric indexes. Serum albumin and transthyretin were also determined for nutritional assessment. RESULTS: Eighty-two randomly selected hemodialysis patients participated in the nutritional assessment, of which 75 hemodialysis patients completed all assessments. The average age was 62.70 ± 14.21 years. The mean duration of hemodialysis was 3.29 ± 1.08 years. Of the included patients, 32% patients were well nourished, 60% were mild to moderately malnourished, and 8% were severely malnourished. Along with the malnutrition severity, the serum transthyretin significantly decreased. However, no obvious changes were found in serum albumin. The mean value (Mean ± SD; 25.78 ± 4.09 cm) of mid arm circumference (MAC) was negatively correlated with MQSGA (r = -0.365; P = 0.002). Body mass index (BMI) (Mean ± SD; 21.6 ± 3.1 kg/m²) was also significantly negatively correlated with MQSGA (r = -0.392; P = 0.001). The areas under the receiver operating characteristic curve were 0.664 and 0.726, respectively. CONCLUSIONS: Malnutrition is very common in South China hemodialysis population. Both BMI and MAC were effective markers for assessing nutritional status.

Controllable inhibition of hepatitis B virus replication by a DR1-targeting short hairpin RNA (shRNA) expressed from a DOX-inducible lentiviral vector.

As a highly efficient delivery system, lentiviral vectors (LVs) have become a powerful tool to assess the antiviral efficacy of RNA drugs such as short hairpin RNA (shRNA) and decoys. Furthermore, recent advanced systems allow controlled expression of the effector RNA via coexpression of a tetracycline/doxycycline (DOX) responsive repressor (tTR-KRAB). Herein, this system was utilized to assess the antiviral effects of LV-encoded shRNAs targeting three conserved regions on the pregenomic RNA of hepatitis B virus (HBV), namely the region coding for the reverse transcriptase (RT) domain of the viral polymerase (LV-HBV-shRNA1), the core promoter (CP; LV-HBV-shRNA2), and the direct repeat 1 (DR1; LV-HBV-shRNA3). Transduction of just the LV-HBV-shRNA vectors into the stably HBV expressing HepG2.2.15 cell line showed significant reductions in secreted HBsAg and HBeAg, intracellular HBcAg as well as HBV RNA and DNA replicative intermediates for all vectors, however, most pronouncedly for the DR1-targeting shRNA3. The corresponding vector was therefore applied in the DOX-controlled system. Notably, strong interference with HBV replication was found in the presence of the inducer DOX whereas the antiviral effect was essentially ablated in its absence; hence, the silencing effect of the shRNA and consequently HBV replication could be strictly regulated by DOX. This newly established system may therefore provide a valuable platform to study the antiviral efficacy of RNA drugs against HBV in a regulated manner, and even be applicable in vivo.

Identification of a Protein Kinase C-dependent phosphorylation site involved in sensitization of TRPV4 channel.

Transient Receptor Potential (TRP) proteins are non-selective cation channels performing diverse cellular functions. TRPV1 and TRPV4, two calcium-permeable channels of the vanilloid subfamily of TRP proteins, are activated by various physical and chemical stimuli, including noxious heat and mechanical stress, respectively. These channels are also required for exaggerated sensation of painful stimuli, condition referred to as hyperalgesia, which is frequently associated with inflammation. Phosphorylation of TRPV1, involving Protein Kinase C (PKC) and Protein Kinase A (PKA), appears to be the predominant mechanism for channel sensitization and development of heat hyperalgesia. PKC and PKA pathways have also been implicated in the sensitization of TRPV4, but the respective phosphorylation sites remain unknown. Using mass spectrometry, we report now that TRPV4 is phosphorylated on serine 824 by the PKC-activating phorbol 12-myristate 13-acetate. This phosphorylation is prevented by a PKC inhibitor, confirming the involvement of PKC. Ser824, located in the carboxy-terminal cytosolic tail of TRPV4, is also phosphorylated after activation of the PKA pathway by forskolin, albeit less potently. Substitution of Ser824 with aspartic acid, mimicking phosphorylation at this site, increased TRPV4-mediated calcium influx in resting and in stimulated cells, underlining the importance of this residue in TRPV4 regulation. Thus PKC, and possibly PKA, phosphorylate TRPV4 at Ser824 leading to the enhancement of TRPV4 channel function. Our findings suggest an important role of this phosphorylation in TRPV4 sensitization and the development of hyperalgesia.

PRKCSH/80K-H, the protein mutated in polycystic liver disease, protects polycystin-2/TRPP2 against HERP-mediated degradation.

Autosomal dominant polycystic liver disease (PCLD) is caused by mutations of either PRKCSH or Sec63, two proteins associated with the endoplasmic reticulum (ER). Both proteins are involved in carbohydrate processing, folding and translocation of newly synthesized glycoproteins. It is postulated that defective quality control of proteins initiates endoplasmic reticulum-associated degradation (ERAD), which disrupts hepatic homeostasis in patients with PRKCSH or Sec63 mutations. However, the precise molecular mechanisms are not known. Here, we show that over-expression or depletion of PRKCSH in zebrafish embryos leads to pronephric cysts, abnormal body curvature and situs inversus. Identical phenotypic changes are induced by depletion or over-expression of TRPP2. Increased PRKCSH levels ameliorate developmental abnormalities caused by over-expressed TRPP2, whereas excess TRPP2 can compensate the loss PRKCSH, indicating that the proteins share a common signaling pathway. PRKCSH binds the C-terminal domain of TRPP2, and both proteins co-localize within the ER. Furthermore, PRKCSH interacts with Herp, and inhibits Herp-mediated ubiquitination of TRPP2. Our findings suggest that PRKCSH functions as a chaperone-like molecule, which prevents ERAD of TRPP2. Dysequilibrium between TRPP2 and PRKCSH may lead to cyst formation in PCLD patients with PRKCSH mutations, and thereby account for the overlapping manifestations observed in PCLD and autosomal dominant polycystic kidney disease.