Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Abstract

Background/Aims: Clinical manifestation and renal histology serve as the current “gold standard” for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. Methods: Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal ­miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-β1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. Results: Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-β1 was inversely correlated (r = –0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. Conclusions: Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-β and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.

Involvement of Circulating Exosomal MicroRNAs in Jian-Pi-Yi-Shen Formula Protection Against Adenine-Induced Chronic Kidney Disease

“…miR-192 prevented renal tubulointerstitial fibrosis in DN rat model by targeting early growth response factor 1 (Egr1) (Liu et al, 2018a). In IgA nephropathy (IgAN), lower serum exosomal miR-192 in IgAN patients correlated with more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (Fan et al, 2019). In addition, urinary miR-192-5p was proposed as a potential biomarker of ischemia/reperfusion-induced kidney injury (Zou et al, 2017).…”

MicroRNAs in IgA nephropathy

“…The degree of tubulointerstitial scarring correlated with miR-205 expression, whereas glomerulosclerosis correlated with miR-192 expression. However, in another study, miR-192 was lower in IgAN patients and it correlated with GFR [42]. Patients with lower intrarenal miR-192 levels had a higher degree of interstitial fibrosis, more severe lesions in tubular atrophy, and interstitial inflammation [42].…”

“…However, in another study, miR-192 was lower in IgAN patients and it correlated with GFR [42]. Patients with lower intrarenal miR-192 levels had a higher degree of interstitial fibrosis, more severe lesions in tubular atrophy, and interstitial inflammation [42]. MiR-233 in glomerular endothelial cells (GEnCs) in IgAN patients correlated with urine protein level, urine erythrocyte count, blood creatinine level, glomerular endothelial proliferation score, and glomerular crescent rate [56].…”

“…Some scholars believe that the inhibition of renal miR-192 could ameliorate renal fibrosis [41]. However, Fan et al [42] showed that lower intrarenal and serum miR-192 levels were related to higher interstitial fibrosis and renal tubular atrophy. The expression levels of renal E-cadherin and TGF-b1 in IgAN negatively correlate with serum miR-192.…”

The Non-Coding RNA Landscape in IgA Nephropathy—Where Are We in 2021?

“…In a similar vein, Fan et al [92] sought to establish a potential association between the intrarenal expression of miR-192 with serum and urinary exosome levels in IgAN patients compared to healthy subjects. They confirmed that intrarenal miR-192 expression correlated with serum levels, eGFR, and with severe interstitial lesions, tubular atrophy and interstitial inflammation.…”