Proteins induced by telomere dysfunction are associated with human IgA nephropathy

Abstract

Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers (cathelin-related antimicrobial peptide (CRAMP), stathmin, elongation factor-1α (EF-1α), and chitinase) were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy (IgAN) progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS), there is no protein upregulation with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine) sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.

Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity

“…This group of proteins is a good predictor of not only human aging but also chronic disease, such as liver fibrosis and myelodysplastic syndrome (MDS). The follow-up studies also showed that among this group of proteins, LL37 is specific for the progression of IgAN [7]. We found higher LL37 expression in renal tissues from IgAN patients, which is also confirmed by IF staining [7].…”

“…The follow-up studies also showed that among this group of proteins, LL37 is specific for the progression of IgAN [7]. We found higher LL37 expression in renal tissues from IgAN patients, which is also confirmed by IF staining [7]. Interestingly, cells with positive LL37 staining were considered to be neutrophils according to their nuclear shape, which led to the hypothesis that neutrophils may participate in the pathology of IgAN.…”

“…Our preliminary study found that LL37 was an aging biomarker induced by DNA damage and telomere dysfunction [6]. LL37 is not only a marker related to IgAN [7] but also an important factor in NETs. Neutrophil infiltration is important in IgAN [27–30].…”

Biomarkers to identify and isolate senescent cells

“…These include cathelin-related antimicrobial peptide (CRAMP), chitinase, stathmin, and EF-1α. Interestingly, one study has shown that CRAMP and chitinase levels highly correlate not only with replicative senescence but also with human aging in general (Lu et al, 2014).…”

The emerging role of cellular senescence in renal diseases

“…Recent studies show that cellular senescence is closely related to glomerular lesions and the degree of glomerular ageing is also related to the progression of nephropathy. 58 For example, during IgA nephropathy (IgAN), disease progression is related to telomere shortening 71 as well as several other senescence-related alterations such as elevated SA-β-gal activity and increased expression of p16 and p21. 72…”