miR‑152 regulates TGF‑β1‑induced epithelial‑mesenchymal transition by targeting HPIP in tubular epithelial cells

Abstract

Renal fibrosis is a common pathological feature of chronic kidney diseases, and their development and progression are influenced by epigenetic modifications including aberrant microRNA (miRNA or miR) expression. miRNAs have been demonstrated to modulate the aggressiveness of various cancers and have emerged as possible therapeutic agents for the management of renal fibrosis. Transforming growth factor β1 (TGF‑β1)‑induced epithelial‑mesenchymal transition (EMT) of tubular epithelial cells serves a role in the initiation and progression of renal fibrosis. Furthermore, recent results indicated that the progression of EMT is reversible. The present study aimed to clarify the role of miR‑152 in EMT of the tubular epithelial cell line HK‑2, stimulated by TGF‑β1, using in vitro transfection with a miR‑152 mimic and to further investigate the underlying mechanism of miR‑152 activity. In the present study, miR‑152 expression was significantly reduced in TGF‑β1‑treated HK‑2 cells, accompanied by an increased expression of hematopoietic pre‑B‑cell leukemia transcription factor (PBX)‑interacting protein (HPIP). Additionally, miR‑152 overexpression inhibited TGF‑β1‑induced EMT and suppressed HPIP expression by directly targeting the 3' untranslated region of HPIP in HK‑2 cells. Furthermore, upregulation of HPIP reversed miR‑152‑mediated inhibitory effects on the EMT. Collectively, the results suggest that downregulation of miR‑152 initiates the dedifferentiation of renal tubules and progression of renal fibrosis, which may provide important targets for prevention strategies of renal fibrosis.

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

“…Zhao et al (2017) found that miR-30c inhibited EMT through Snail1-TGF-β1 pathway, and attenuated diabetic nephropathy. In another study, researchers found that miR-152 overexpression inhibited TGF-β1-induced EMT in HK-2 cells (Ning et al, 2018). It is hard to identify which miRNA determines EMT initiation, and some have suggested unbalanced control of several miRNAs.…”

Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study

“…This trend was confirmed by the reduced expression of miR-152-3p in B. vulgatus -A2 CFS-treated organoids from PCeD. Even if miR-152-3p has a positive effect on CeD signaling pathways in different pathological contexts, 49 , 50 to the best of our knowledge, no studies have been reported in literature that specifically correlate this miRNA to CeD. Interestingly, in our dataset miR-152-3p is the only miRNA to be significantly modulated in PCeD versus HC organoids at basal condition.…”

miR−122−5p Regulates Renal Fibrosis In Vivo

“…Previously, several miRNAs were reported to be associated with renal fibrosis [ 3 , 13 , 14 , 15 , 16 , 17 , 18 ]—the expression levels of miR−21, −22, −135a, −150, −155, −184, −214, −215, −216a, −324, −433, and −1207 were upregulated in fibrotic kidneys [ 18 , 29 , 30 , 31 , 32 ]. In contrast, the expression levels of let-7, miR−29, −30, −34, −152, −181, −194, −200, and −455 were downregulated in fibrotic kidneys [ 18 , 21 , 33 , 34 , 35 ]. In this study, we confirmed that the expression levels of three miRNAs (miR−511−3p, −375−3p, and −127−3p) were significantly upregulated, and the expression levels of three miRNAs (miR−122−5p, −504−3p, and −363−3p) were significantly downregulated, in fibrotic kidneys by qRT−PCR.…”