Glomerular microthrombosis (GMT) was a common vascular lesion in patients with lupus nephritis (LN). The objective of this study was to investigate the relationship between serum ...anti-beta2-glycoprotein I antibodies (a-β2GP1) and anti-complement 1q antibodies (a-C1q) antibodies and to investigate the possible mechanism of GMT in children with LN.
The subjects were 191 children with LN diagnosed by renal biopsy in our hospital from January 2017 to January 2020. The patients were divided into GMT group and non-GMT group. The clinical manifestations, laboratory tests, renal pathology, prognosis of the two groups and the relationship between a-β2GP1 and a-C1q antibodies were observed.
In 191 children with LN, 52 cases (27.23%) presented with GMT. The value of C3, haemoglobin (Hb), estimate glomerular filtration rate (eGFR) and anticardiolipin antibody (ACA) in GMT group were lower than that of non-GMT group (p < .05, p < .01). The value of serum creatinine (Scr), 24 h proteinuria (PRO), urine red blood cells (RBC), N-acetyl-β-d-glucosidase (NAG) and retinol-binding protein (RBP), a-C1q, a-β2GP1, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal histopathological activity index (AI) score in GMT group were higher than that of non-GMT group (p < .05, p < .01). The positive proportions of serum a-C1q and a-β2GP1 in GMT group were higher than those in non-GMT group (p < .05). According to Spearman correlation analysis, a-C1q was positively correlated with AI score, SLEDAI, a-β2GP1, GMT, LN-III and LN-IV. Hb, eGFR and a-C1q Ab were associated with the formation of GMT in children with LN. The complete proteinuria remission and renal survival in GMT group were significantly lower than those in non-GMT group (p < .05, p < .01).
LN children with GMT had more severe clinical manifestations and renal pathologic damages, and poor outcome. Serum a-C1q level was positively correlated with a-β2GP1, and a-β2GP1 may be involved in the formation of GMT in children with LN, which might involve in the activation of complement classical pathway.
Curcumin can regulate the polarization of microglia and alleviate traumatic brain injury (TBI). However, its detailed action mechanism on downregulating Complement 1q-like-3 protein (C1ql3) in TBI is ...less reported. The purpose of this study is to explore the role and mechanism of curcumin-regulated C1ql3 in TBI.
GSE23639 dataset was used to acquire gene data for microglia. C57BL/6 J wild-type (WT) mice were subjected to establish a controlled cortical impact model of TBI. The effects of curcumin (200 mg/kg) on the brain injury, inflammatory cytokine levels, microglia polarization, and C1ql3 protein expression in mice and BV-2 cells were detected by H&E staining, qRT-PCR, immunofluorescence, and Western blot, respectively. The effects of curcumin (5, 10, 20 μmol/L) and lipopolysaccharides (LPS, 1 µg/mL) on the viability of BV-2 cells were determined by MTT assay. After the transfection of C1ql3 overexpression plasmid, C1ql3 expression, IL-1β and IL-6 levels, and the number of CD16+/32+ and CD206+ cells were determined by qRT-PCR, ELISA and flow cytometry, respectively.
C1ql3 expression was down-regulated in microglia after the curcumin treatment. Curcumin treatment could alleviate the TBI-induced brain injury in mice, reduce IL-1β and IL-6 levels, promote M2 polarization of microglia, and decrease C1ql3 protein expression. For BV-2 cells, curcumin treatment had no significant toxic effect on cell viability, but reversed the effect of LPS on cells, while C1ql3 overexpression counteracted the effect of curcumin.
Curcumin induces M2 microglia polarization through down-regulating C1ql3 expression, which may become a new treatment method for TBI.
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
•C1ql3 was down-regulated in microglia after the curcumin treatment.•Curcumin treatment reduced the IL-1β and IL-6 levels, promoted M2 polarization in mice microglia and BV-2 cells.•C1ql3 overexpression reversed the effect of curcumin treatment, it induced inflammation and M1 polarization in BV-2 cells.•Curcumin treatment alleviated TBI through suppressing the C1ql3 expression.
Complement 1q-binding protein (gC1qR), a multi-functional cellular protein, is able to bind the globular head region of C1q molecule (gC1q), playing an important role in regulation of immune response ...and host defense against bacterial infection. In this study, the full length of a gC1qR ortholog (OngC1qR) was identified and characterized from Nile tilapia (Oreochromis niloticus). The cDNA of OngC1qR ORFs consisted of 870 bp of nucleotide sequence encoding a 289 amino acid residue polypeptide. The deduced amino acid sequence is highly homologous to teleost, containing a MAM33p domain, two potential glycosylation sites, and a putative cell adhesion site EGD (Glu-Gly-Asp). Spatial mRNA expression analysis revealed that the OngC1qR was expressed ubiquitously in all examined tissues, with a high expression in the liver. The OngC1qR expression was significantly up-regulated in liver, spleen and head kidney following in vivo challenges with Streptococcus agalactiae. A high up-regulation was also detected in head kidney leukocytes in vitro stimulation with Streptococcus agalactiae. In addition, immunofluorescence detection illustrated that the OngC1qR was located at the cell surface of leukocytes. Recombinant OngC1qR protein was able to not only bind LPS, LTA, S. agalactiae and Aeromonas hydrophila, but also possess binding capability with the ligand OnC1qs. Taken together, the results indicated that OngC1qR might be involved in host defense against bacterial infection in Nile tilapia.
•Full-length cDNA of gC1qR was identified and characterized in Nile tilapia.•Expressions of OnC1qR were significantly up-regulated upon LPS and bacterial challenges.•OnC1qR was located on the surface of leukocytes.•Recombinant OnC1qR was able to bind bacteria and ligand OnC1qs.
To observe the effect of electroacupuncture (EA) of "Xiusanzhen" ［bilateral "Yingxiang"(LI20)+"Yintang"(GV24
)］ on synaptophysin (SYN), postsynaptic density protein-95 (PSD-95), Iba-1
CD68
microglia ...and complement C related protein expression of hippocampus in Parkinson's disease dementia (PDD) mice, so as to explore its mechanism in improving memory impairment of PDD.
Male C57BL/6 mice were randomly divided into control, sham operation, model and EA groups, with 10 mice in each group. The PDD model was established by injecting 6-OHDA into the medial forebrain tract. EA (2 Hz, 1 mA) was applied to unilateral LI20 and GV29 for 20 min once daily for consecutive 14 days. Morris water maze and new object recognition test were used to evaluate the learning and memory ability. Western blot was used to detect the expression of SYN and PSD-95 proteins in hippocampus. Immunofluorescence was used to label Iba-1
CD68
microglia and C1q positive cells in hippocampal CA1 region. The content of C3 protein in hippocampus was
Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies ...focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138
cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21). CD138
cells expressed higher levels of C1q receptors (C1qRs) than CD138
cells. Patients with Amp1q21 expressed higher levels of globular C1qR (gC1qR), whereas patients without Amp21 expressed higher levels of collagen tail C1qR (cC1qR). Additionally, gC1qR was noted to suppress the MM-inhibiting role of C1q in H929, U266, and MM1S. gC1qR interacts with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which also suppressed the function of C1q and regulated CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA. In summary, gC1qR suppressed the MM-inhibiting role of C1q and regulated CKS1B mRNA in promoting tumor proliferation via IGF2BP3 in 1q21-amplified MM. Our findings provide novel evidence on how MM cells evade the immune system and promote survival as well as suggest possible novel targets for future therapies of MM.
Lupus nephritis (LN) is a kidney disorder that is a critical cause of mortality in patients with systemic lupus erythematosus. The present study aimed to explore the protective role of complement ...component 1q (C1q) on LN and the underlying mechanism involving the nuclear factor (NF)‑κB singling pathway. MRL/lpr mice served as the LN mouse model, and pcDNA‑C1q was injected into LN mice to determine the role of C1q. C1q mRNA expression was detected using reverse transcription‑quantitative PCR. Urine protein and blood urea nitrogen (BUN) levels were measured, and the histological damage index was determined using H&E staining. ELISA was used to measure the levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β, IL‑6, anti‑C1q and anti‑double stranded DNA (dsDNA). CD68‑ and Ki67‑positivity were detected using immunofluorescence, and NF‑κB‑related protein expression was examined using western blotting. C1q mRNA expression was downregulated in renal tissues of LN mice. Overexpression of C1q decreased urine protein, BUN levels and the histological damage index in LN mice. The levels of TNF‑α, IL‑1β, IL‑6, anti‑C1q and anti‑dsDNA in renal tissues of LN mice were also reduced after pcDNA‑C1q treatment. Additionally, overexpression of C1q decreased the CD68‑ and Ki67‑positivity in glomeruli and attenuated the expression of NF‑κB‑related proteins. Phorbol 12‑myristate 13‑acetate, an NF‑κB pathway activator, reversed the inhibitory effect of C1q on inflammation, macrophage infiltration and mesangial cell (MC) proliferation in renal tissues of LN mice. Thus, it was demonstrated that C1q ameliorated inflammation and macrophage infiltration and decreased MC proliferation in renal tissues of LN mice by inhibiting the NF-κB pathway.
C1Q (Complement 1Q) is an important recognition molecule in the immunological complement system, which could also be putatively involved in the stress responses induced by endotoxins or exotoxins, ...potentially through detoxification processes. Marine bivalves are well adapted to highly complex aquatic environments with various stressors. As filter feeders, they have to cope with highly potent microalgae-derived neurotoxins, such as paralytic shellfish toxin (PSTs). Zhikong scallops,
Chlamys farreri
, are commercially important bivalve with the remarkable ability to accumulate PSTs. Exploring the
C1Q
s related to PST accumulation in
C. farreri
could benefit our understanding of the adaptations of bivalve species. In the present study, we systematically analyzed
C1Q
genes in
C. farreri
. In total, 97
CfC1Q
genes mainly from the expanded C1Q-B subfamily were identified, from which the
C1QL
,
C1QTNF
, and
C1QDC1
members in
C. farreri
were revealed to be under positive selection. Spatiotemporal expression analysis revealed that most
CfC1QL
s and
CfC1QDC1
s were highly expressed during the post-umbo stage and in hepatopancreas, while most
CfC1QTNF
members were highly expressed after the creeping larva stage and in mantle. The hepatopancreas and kidney in
C. farreri
are two toxin-rich organs with the highest concentrations of PSTs, acting as major “centers” for toxin accumulation and transformation, respectively. Therefore, after feeding the scallops with PST-producing dinoflagellates
Alexandrium minutum
and
Alexandrium catenella
, we determined the expression patterns of
CfC1Q
s in these two organs. In kidney, more than 85% of
CfC1QL
s and
CfC1QDC1
s showed drastic up-regulation with both diets. However, among these members with significant induction, a different response manner was detected after feeding with
A. minutum
and
A. catenella
, respectively as acute and chronic response patterns. In comparison, far fewer
CfC1Q
s showing significant up-regulation in hepatopancreas with both toxic diets and only mild regulation pattern could be found. This organ-, toxin-, and time-dependent genetic regulation of
CfC1Q
s may contribute to the virulence difference on account of the tissue-specific or dinoflagellate-specific different toxin analogs composition, implying the possible involvement of
CfC1Q
s in PST transport and homeostasis. Our findings imply the functional diversity of scallop
C1Q
genes in coping with PST accumulation, which might be developed as potential molecular indicators for monitoring toxin accumulation in edible mollusks or provide insight into the lineage-specific adaptation of scallops for dealing with microalgal toxin challenges.
Systemic lupus erythematosus (SLE) is characterized by excessive production of various autoantibodies, which play important roles in the pathogenesis of SLE. Apart from classical autoantibodies such ...as anti-double stranded DNA antibody (anti-dsDNA), anti-Smith antibody (anti-Sm), and anti-phospholipid antibody (APL), recent studies focus on some novel autoantibodies including anti-complement (C) 1q antibody (anti-C1q), which is closely correlated with lupus nephritis; anti-N-methyl-
d
-asparate receptor antibody (NMDAR), which mediates neuropsychiatric manifestations in SLE to some extent; anti-galectin, which is involved in secondary anti-phospholipid syndrome (APS) in SLE; and anti-Müllerian hormone (AMH), which represents a more specific biomarker for subclinical ovarian damage caused by the disease itself or cytotoxic drugs in SLE patients. Correlation of these autoantibodies with disease activity and organ involvement of SLE may help to evaluate disease severity, efficacy of treatment, and long-term prognosis. Furthermore, combined measurement of a variety of autoantibodies is supposed to be more valuable in estimating disease activity and severity.
Aims/Introduction
As a member of the tumor necrosis factor‐α‐related protein family, complement‐1q tumor necrosis factor‐α‐related protein isoform 5 (CTRP5) has been found to be associated with ...obesity and insulin resistance (IR). Previous studies in humans and animals have reported contradictory results related to the association between CTRP5 and IR. The purpose of the present study was to explore the relationship between CTRP5 and IR through a cross‐sectional study and drug intervention study of type 2 diabetes patients.
Materials and Methods
A cross‐sectional study was carried out with 118 newly diagnosed patients with type 2 diabetes and 116 healthy adults. In an interventional study, 78 individuals with newly diagnosed type 2 diabetes received sodium–glucose cotransporter 2 inhibitor (dapagliflozin) treatment for 3 months. Circulating CTRP5 concentrations were measured by enzyme‐linked immunosorbent assay.
Results
Serum CTRP5 concentrations were markedly reduced in patients with type 2 diabetes when compared with those of healthy individuals (P < 0.01). When considering the study population as a whole, individuals with IR (homeostasis model of assessment of IR ≥2.78) had lower CTRP5 concentrations than the individuals without IR (homeostasis model of assessment of IR <2.78; P < 0.01). Serum CTRP5 negatively correlated with age, body mass index, waist‐to‐hip ratio, Systolic blood pressure, triglyceride, total cholesterol, glycated hemoglobin, fasting blood glucose, 2‐h blood glucose, fasting insulin and homeostasis model of assessment of IR. After 12 weeks of sodium–glucose cotransporter 2 inhibitor treatment, serum CTRP5 levels in type 2 diabetes patients were significantly reduced accompanied with ameliorated glycometabolism and IR compared with before treatment (P < 0.01).
Conclusions
CTRP5 is likely a marker for type 2 diabetes in humans.
The present study found that complement‐1q tumor necrosis factor‐α‐related protein isoform 5 (CTRP5) levels were reduced in type 2 diabetes patients and that plasma CTRP5 levels were related to insulin resistance. Furthermore, we found that plasma CTRP5 concentrations further decreased after dapaglifozin treatment, which showed that CTRP5 might play an important role in the development of type 2 diabetes.
Inflammation induced by circulating immunoglobulin G–immune complexes (ICs) characterizes many immune-mediated diseases. In this work, the molecular requirements for the deposition of circulating ICs ...and subsequent acute leukocyte recruitment in mice were elucidated. We show that after intravenous injection, preformed soluble ICs are rapidly deposited in the postcapillary venules of the cremaster microcirculation, secondary to increased vascular permeability. This deposition is dependent on complement C1q. IC deposition is associated with leukocyte recruitment. Leukocyte rolling, which is mediated by P-selectin in the exteriorized cremaster muscle, is not further increased in response to ICs. In contrast, leukocyte rolling velocity is significantly decreased and leukocyte adhesion is significantly increased in the presence of ICs. The IC-mediated slow leukocyte rolling velocity and subsequent adhesion and emigration are dependent on Fcγ receptors (FcγRs), particularly FcγRIII, with complement C3 and C5 having no detectable role. These studies suggest a regulatory mechanism of IC deposition and leukocyte trafficking in IC-mediated inflammation requiring C1q and FcγRs in sequential, noninteracting roles.
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