miR-30c-5p Reduces Renal Ischemia-Reperfusion Involving Macrophage

Abstract

Background Ischemia-reperfusion (I/R) leads to kidney injury. Renal I/R frequently occurs in kidney transplantations and acute kidney injuries. Recent studies reported that miR-30 stimulated immune responses and reductions in renal I/R related to anti-inflammation. Our study investigated the effects of miR-30c-5p on renal I/R and the relationship among miR-30c-5p, renal I/R, and macrophages. Material/Methods Sprague Dawley rats received intravenous tail injections of miR-30c-5p agomir. Then a renal I/R model were established by removing the left kidney and clamping the right renal artery. Serum creatinine (Cr) was analyzed using a serum Cr assay kit, and serum neutrophil gelatinase associated lipocalin (NGAL) was measured using a NGAL ELISA (enzyme-linked immunosorbent assay) kit. Rat kidney tissues were analyzed using hematoxylin and eosin staining. THP-1 cells treated with miR-30c-5p agomir and miR-30c-5p antagomir were measured with quantitative reverse transcription-polymerase chain reaction. Protein levels were analyzed by western blot. Results MiR-30c-5p agomir reduced serum Cr, serum NGAL, and renal I/R injury. MiR-30c-5p agomir inhibited the expression of CD86 (M1 macrophage marker), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-α) and promoted the expression of CD206 (M2 macrophage marker), interleukin (IL)-4, and IL-10 in rat kidneys. MiR-30c-5p agomir reduced the expression of CD86 and iNOS, and increased the expression of CD206 and IL-10 in THP-1 cells. Conclusions We preliminarily demonstrated that miR-30c-5p agomir might decrease renal I/R through transformation of M1 macrophages to M2 macrophages and resulted in changes in inflammatory cytokines.

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

“…miR-30: As described ahead, miR-30 preserved mitochondrial morphology and inhibited cell apoptosis in I/R-induced AKI rat model [24]. miR-30c has been shown to target Bnip3L and Hspa5, thereby inhibiting cisplatin-induced tubular epithelial cell apoptosis [48]. In addition, He et al reported that miR-30a is associated with the inhibition of UUO-induced renal fibrosis under MSC-EVs treatment [28].…”

“…The mechanism regulating cell apoptosis is one of the most important aspects of renal protection. Indeed, the anti-apoptotic pathway has been reported in many studies with MSC-EVs treatment in a variety of rodent renal injury models, including AKI induced by I/R [24,31,33,104,106,[116][117][118]120,124,125], cisplatin [48,119,126], gentamicin [105], and glycerol [17], hypoxia-induced renal injury [60], aldosterone-induced renal injury [52], and UUO-induced CKD model [109]. Recent advances have gradually uncovered the specific miRNAs, their targets and signaling pathways involved in the effect of anti-apoptosis (Table 2), including PTEN, AKT, mTOR, dynamin-related protein 1 (DRP1), Sema3A, and ERK signaling pathway.…”

Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation

“…Yang et al (2020) showed that the M2 polarization of tumor-associated macrophages could be promoted by long noncoding RNA (lncRNA) RP11-361F15.2 through miR-30c-5p. A miR-30c-5p agomir might contribute to the transformation of M1 macrophages to M2 macrophages, resulting in changes in inflammatory cytokine levels (Zhang et al, 2019). A recent study showed that miR-16-5p mimics significantly decreased the mRNA expression of IL-1β, IL-6, and TNF-α under LPS stimulation conditions, which indicated that miR-16-5p might be a critical factor involved in the antiinflammatory effects (Yamada et al, 2020).…”

miR-30c-5p Alleviated Pyroptosis During Sepsis-Induced Acute Kidney Injury via Targeting TXNIP

“…Another study also determined that miR-204 reduce the IL-6R expression to alleviate LPS-induced mesangial cell apoptosis and oxidative stress accumulation in SAKI [ 13 ]. Of interest, miR-30c-5p, which has been proved as an essential mediator of kidney injury, was able to inhibit the expression of tumor necrosis factor-alpha (TNF-α) and multiple inflammatory cytokines in rats [ 14 , 15 ]. Overexpression of miR-30c-5p could also significantly increase human renal tubular epithelial cells (HK-2 cells) apoptosis to inhibit kidney stones formation [ 16 ].…”