Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Abstract

Membranous nephropathy (MN) is a renal-limited non-inflammatory autoimmune disease in the glomerulus, which is the second or third main cause of end-stage kidney diseases in patients with primary glomerulonephritis. Substantial achievements have increased our understanding of the aetiology and pathogenesis of murine and human MN. The identification of nephritogenic autoantibodies against neutral endopeptidase, phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by specific B cell-targeting monoclonal antibodies to inhibit antibody production and antibody-antigen immune complex deposition. Furthermore, additional antibody specificities for antigens have been discovered, but their pathogenic effects are uncertain. Although anti-PLA2R and anti-THSD7A antibodies as a diagnostic marker is widely used in MN patients, many questions including autoimmune response development, antigenic epitopes, and podocyte damage signalling pathways remain unresolved. This review describes the current available evidence regarding both established and novel molecular mechanisms based on systems biology approaches (gut microbiota, long non-coding RNAs, metabolite biomarkers and DNA methylation) in MN, with an emphasis on clinical findings. This review further summarizes the applications of traditional Chinese medicines such as Tripterygium wilfordii and Astragalus membranaceus for MN treatment. Lastly, this review considers how the identification of novel antibodies/antigens and unresolved questions and future challenges reveal the pathogenesis of MN.

TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis

“…Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease, which was associated with a various molecular mechanisms such as activations of aryl hydrocarbon receptor [106][107][108][109][110], NF-κB [111,112] and Wnt/β-catenin [113][114][115] signalling pathways as well as dysbiosis of gut [116,117] and disorder of endogenous metabolite [118][119][120][121][122]. Kidney aging has been identified as a chronic process characterized by impaired renal function and structural changes in the tubular interstitium and glomerulus [123].…”

Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan‐produced indole metabolites

“…Based on the metagenomic technique, one publication has uncovered that the relative abundance of Lactobacillus vaginalis , Lactobacillus reuteri , Subdoligranulum variabile , Bacteroides vulgatus and Prevotella copri was associated with changes in serum levels of albumin, total cholesterol and triglyceride, and protein expression of intrarenal immunoglobulin G (IgG) and complement 3 (C3) in rats with passive Heymann nephritis (Wang, Yang, et al, 2022). In addition, several publications have shown microbial dysbiosis in faecal samples from IMN patients when using 16S rRNA sequence analysis (Miao, Zhang, et al, 2022). Megasphaera , Megamonas , Akkermansia , Lachnospira , Roseburia and Fusobacterium exhibited a relatively‐high abundance in healthy controls compared to IMN patients (Zhang et al, 2020).…”

“…Additionally, Boulange et al reported urine levels of significantly decreased creatinine, citrate, hippurate and phenylacetate in patients with IMN (Boulangé et al, 2019). However, few studies have reported the identification of microbial‐derived metabolites in MN (Miao, Zhang, et al, 2022) although, based on combining high‐throughput sequencing analysis and untargeted metabolomics, a previous publication has shown association between microbiota and metabolites in CKD (Wang et al, 2020).…”

BaoShenTongLuo formula protects against podocyte injury by regulating AMPK-mediated mitochondrial biogenesis in diabetic kidney disease

“…Increasing numbers of studies have shown that traditional Chinese medicines (TCMs) have been widely utilized to treat patients, and TCMs have been proved to be useful in the treatment of a number of renal diseases [ 14 – 19 ]. BSTL is a TCM prescription that is composed of Astragalus membranaceus (Huangqi), Rehmannia glutinosa (Dihuang), Cuscuta chinensis (Tusizi), Artemisia Anomala (Liujinu), Euonymus alatus (Guijianyu), Hirudo (Shuizhi) and Salvia Miltiorrhiza Bunge (Danshen).…”