TABLE 1.
Cell‐type‐enriched EV miRNA also detected in human urinary extracellular vesicles
| miRNA | Functions associated to disease | Association with kidney disease | References |
|---|---|---|---|
| Podocytes | |||
| miR‐204‐5p | highly expressed in the kidney; miR‐204‐5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury; urinary exosomal level as biomarker for Xp11.2 translocation renal cell carcinoma | yes | (Cheng et al., 2020; Kurahashi et al., 2019) |
| miR‐99b‐5p | miR‐99b‐5p is associated with response to tyrosine kinase inhibitor treatment in clear cell renal cell carcinoma patients | yes | (Lukamowicz‐Rajska et al., 2016) |
| miR‐194‐5p | miR‐194‐5p was significantly downregulated in patient urine exosomes, in murine Pkd1 cystic kidneys and in human PKD1 cystic kidney tissue | yes | (Magayr et al., 2020) |
| miR‐99a‐5p | miR‐99a‐5p was upregulated in macro‐albuminuric patients compared with normo‐albuminuric and micro‐albuminuric patients. Transfection of miR‐99a‐5p in cultured human podocytes downregulated mTOR protein expression and downregulated the podocyte injury marker vimentin | yes | (Uil et al., 2021) |
| miR‐425‐5p | miR‐425‐5p is a potential predictor of extreme response to tyrosine kinase inhibitors in renal cell cancer | yes | (Garrigós et al., 2020) |
| miR‐99b‐3p | miR‐99b‐3p promotes angiotensin II‐induced cardiac fibrosis in mice by targeting GSK‐3β | no | (Yu et al., 2021) |
| miR‐625‐3p | miR‐625‐3p promotes migration and invasion and reduces apoptosis of clear cell renal cell carcinoma | yes | (Zhao et al., 2019) |
| miR‐625‐5p | involved in regulation of Wnt/β‐catenin and NF‐kappa‐B activation | no | (Tang et al., 2019) |
| miR‐503‐5p | miR‐503‐5p functions as an oncogene in various cancer diseases, such as oral squamous cell carcinoma | no | (Fei et al., 2020) |
| miR‐15a‐5p | decreased urinary exosomal level in incipient T2D kidney disease | yes | (Xie et al., 2017) |
| Mesangial cells | |||
| let‐7b‐5p | TGF‐β1‐regulated miRNA which is associated with an increased risk of rapid progression to end‐stage renal disease | yes | (Pezzolesi et al., 2015) |
| miR‐200a‐3p | MicroRNA‐200a‐3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma | yes | (Wang et al., 2016) |
| miR‐429 | increased urinary exosomal level upon acute kidney injury | yes | (Sonoda et al., 2019) |
| miR‐101‐3p | potential earyl biomarker for acute kidney injury | yes | (Aguado‐Fraile et al., 2015) |
| miR‐664a‐5p | decreased serum exosomal level in patients with pancreatic ductal adenocarcinoma | no | (Wang et al., 2021) |
| miR‐181a‐5p | miR‐181a‐5p regulates the proliferation and apoptosis of glomerular mesangial cells by targeting KLF6 | yes | (X. Liang & Xu, 2020) |
| let‐7b‐3p | involved in the pathogenesis of chronic thromboembolic pulmonary hypertension | no | (Gong et al., 2021) |
| miR‐542‐3p | MiR‐542‐3p drives renal fibrosis by targeting AGO1 in vivo and in vitro | yes | (Li et al., 2020) |
| miR‐200a‐5p | increased urinary exosomal level upon acute kidney injury; miR‐200a Prevents renal fibrogenesis through repression of TGF‐β2 expression | yes | (Sonoda et al., 2019; Wang et al., 2011) |
| miR‐3605‐3p | miscellaneous | no | |
| Proximal tubule cells | |||
| miR‐532‐5p | miR‐532‐5p suppresses renal cancer cell proliferation by disrupting the ETS1‐mediated positive feedback loop with the KRAS‐NAP1L1/P‐ERK axis; increased urinary exosomal miR‐532‐5p level in intermediate‐risk prostate cancer | yes | (Kim et al., 2021; Zhai et al., 2018) |
| miR‐95‐3p | invoved in angiogenesis; increased in ectosomes obtained from patients with T2D | no | (Stępień et al., 2018) |
| miR‐31‐5p | miR‐31‐5p acts as a tumor suppressor in renal cell carcinoma by targeting cyclin‐dependent kinase 1 | yes | (Li et al., 2019) |
| miR‐187‐3p | Mesenchymal Stem/Stromal Cells Increase Cardiac MIR‐187‐3P Expression in Polymicrobial Animal Model of Sepsis | no | (Ektesabi et al., 2021) |
| miR‐218‐5p | miR‐218‐5p is expressed in endothelial progenitor cells and contributes to the development and repair of the kidney microvasculature | yes | (Wang et al., 2020) |
| miR‐181a‐2‐3p | miR‐181a‐2‐3p alleviates the apoptosis of renal tubular epithelial cell via targeting GJB2 in sepsis‐induced acute kidney injury | yes | (Yi et al., 2021) |
| miR‐185‐5p | miR‐185‐5p ameliorates endoplasmic reticulum stress and renal fibrosis by downregulation of ATF6 | yes | (Yuan et al., 2020) |
| miR‐708‐5p | considered as a therapeutic agent against metastatic lung cancer | no | (Wu et al., 2016) |
| miR‐130a‐3p | miR‐130a‐3p inhibition protects against renal fibrosis in vitro via the TGF‐β1/Smad pathway by targeting SnoN | yes | (Ai et al., 2020) |
| miR‐335‐3p | aldosterone regulates miR‐335‐3p in the cortical collecting duct to alter sodium transport | yes | (Edinger et al., 2014) |
| miR‐500a‐5p | involved in epithelial‐mesenchymal transition | no | (Tang et al., 2020) |
| miR‐500b‐5p | involved in phenotypic switching in vascular smooth muscle cells and is involved in the pathogenesis of aortic dissection. | no | (Wang et al., 2021) |
| Glomerular endothelial cells | |||
| miR‐125b‐5p | decreased urinary exosomal miRNA level in individuals with diabetic kidney disease | Yes | (Zang et al., 2019) |
| miR‐10b‐5p | miR‐10a‐5p has been associated with disease progression, proliferation and invasion of renal cell carcinoma | yes | (Kowalik et al., 2017) |
| miR‐29a‐3p | acts anti‐fibrotic, mainly by targeting different types of collagen via a Smad3‐dependent mechanism, thus leading to decreased ECM accumulation; Linagliptin, a DPP‐4 inhibitor used as an anti‐diabetic drug, can also confer renal protection and decrease fibrosis in a mouse model of DN by inducing miR‐29a, which targets DPP‐4 | yes | (Assmann et al., 2018; Kanasaki et al., 2014) |
| miR‐29c‐3p | acts anti‐fibrotic, mainly by targeting different types of collagen via a Smad3‐dependent mechanism, thus leading to decreased ECM accumulation; linagliptin and telmisartan‐induced restorative effects on miR‐29c expression were reflected in urinary exosomes | yes | (Assmann et al., 2018; Delić et al., 2020) |
| miR‐29b‐3p | acts anti‐fibrotic, mainly by targeting different types of collagen via a Smad3‐dependent mechanism, thus leading to decreased ECM accumulation | yes | (Assmann et al., 2018) |
| miR‐199a‐3p | acts as a tumor suppressor in clear cell renal cell carcinoma and acts in a pro‐fibrotic manner in chronic diabetic kidney disease; telmisartan and linagliptin suppressed the induction of miR‐199a‐3p | yes | (Delić et al., 2020; Liu et al., 2018) |
| miR‐199b‐3p | miscellaneous | no | |
| miR‐361‐5p | involved in regulation of epithelial‐mesenchymal transition | no | (Yin et al., 2020) |
| miR‐107 | increased urinary exosomal miRNA level in clinical responders (lupus nephritis patients) | yes | (Garcia‐Vives et al., 2020) |
| miR‐221‐3p | increased urinary level after drug‐induced kidney injury | yes | (Chorley et al., 2021) |
| miR‐660‐5p | miR‐660‐5p is associated with cell migration, invasion, proliferation and apoptosis in renal cell carcinoma | yes | (He et al., 2018) |
| miR‐532‐3p | decreased expression in kidneys obtained from patients with progressive chronic kidney disease | yes | (Rudnicki et al., 2016) |
| miR‐501‐3p | high expression levels of exosome miR‐501‐3p contribute to arteriosclerotic changes | no | (Toyama et al., 2021) |
| miR‐500a‐3p | miR‐500a‐3P alleviates kidney injury by targeting MLKL‐mediated necroptosis in renal epithelial cells | yes | (L. Jiang et al., 2019) |
| miR‐10b‐3p | miscellaneous | no | |
| miR‐126‐3p | relevant for DKD pathogenesis and endothelial to mesenchymal transition | yes | (Wang et al., 2019) |
| miR‐19b‐3p | exosomal miRNA‐19b‐3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury | yes | (Lv et al. 2020) |
| miR‐20a‐5p | miR‐20a‐5p is enriched in hypoxia‐derived tubular exosomes and protects against acute tubular injury | yes | (Yu et al., 2020) |
| miR‐185‐5p | reduces endoplasmic reticulum stress and fibrosis in vitro and in a mouse model of kidney fibrosis. | yes | (Yuan et al., 2020) |
| miR‐760 | increased urinary exosomal microRNA signatures in nephrotic, biopsy‐proven DN | yes | (Lee et al., 2020) |
| miR‐324‐5p | miR‐324‐5p inhibits lipopolysaccharide‐induced proliferation of rat glomerular mesangial cells by regulating the Syk/Ras/c‐fos pathway | yes | (Wang et al., 2020) |
| miR‐195‐5p | miR‐195‐5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A | yes | (Chen et al., 2017) |
Note: Functions associated with disease (reported in bibliography).
Abbreviations: AGO1, argonaute RISC component 1; ATF6, activating transcription factor 6; COL I/III, collagen I/III; DKD, diabetic kidney disease; DPP‐4, dipeptidyl peptidase‐4; ECM, extracellular matrix; ETS1, ETS proto‐oncogene 1; GJB2, gap junction protein beta 2; GSK‐3β, glycogen synthase kinase 3 beta; KLF6, Kruppel Like factor 6; KRAS, KRAS proto‐oncogene; MLKL, mixed lineage kinase domain like pseudokinase; mTOR, mammalian target of rapamycin; NAP1L1, nucleosome assembly protein 1 like 1; NF‐kappa‐B, nuclear factor kappa beta; P‐ERK, phospho‐ERK; Pkd1, polycystic kidney disease 1; SnoN, nuclear Smad‐interacting protein; SPAG9, sperm associated antigen 9; Syk, spleen associated tyrosine kinase; T2D, Type 2 diabetes; TGF‐β1, transforming growth factor beta 1; TGF‐β2, transforming growth factor beta 2.