Renal fibrosis is a key factor in chronic kidney disease (CKD). Long non-coding RNAs (lncRNAs) play important roles in the physiological and pathological progression of human diseases. However, the roles and underlying mechanisms of lncRNAs in renal fibrosis still need to be discovered. In this study, we first displayed the increased lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in renal fibrosis in patients with obstructive nephropathy (ON). Then we found that transforming growth factor beta 1 (TGF-β1) induced epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) protein deposition, which promoted the viability, proliferation and migration of human renal proximal tubular epithelial (HK2) cells. Next, MALAT1/miR-145/focal adhesion kinase (FAK) pathway was confirmed to play an importment role in TGF-β1induced renal fibrosis. In addition, the MALAT1/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-β1-induced renal fibrosis in vitro and in vivo. Furthermore, m 6 A methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of m 6 A modification on MALAT1.

Context: Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects. Objective: To explore the mechanisms underlying the effects of curcumin on RIF. Materials and methods: Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-b1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation. Results: In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1b and TNF-a by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and a-smooth muscle actin in TGF-b1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1b and TNF-a by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF-jB and p-IjBa in both LPS-and TGF-b1induced HK-2 cells. Discussion and conclusions: Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-jB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.

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Renal fibrosis, the ultimate common pathway of progressive nephropathy, is characterized by excess accumulation and deposition of extracellular matrix (ECM) within the renal interstitium and glomeruli, finally resulting in end‐stage kidney failure. TGFβ1 is not only abnormally increased during fibrosis but also involved in ECM induction and accumulation. Based on the bioinformative analyses, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and focal adhesion kinase (FAK) signaling pathway might be involved in TGFβ1 functions on renal fibrosis development. In the present study, fibrosis was induced in HK‐2 cells using TGFβ1 and PTEN expression was significantly suppressed by 24 or 48 hours TGFβ1 treatment. PTEN overexpression in HK‐2 cells improved TGFβ1‐induced fibrosis within α‐SMA and E‐cadherin. According to the KEGG signaling pathway annotation analyses on microarray profiles (GSE23338 and GSE20247) and immunoblotting validation, FAK signaling might be involved in PTEN functions in TGFβ1‐induced fibrosis. PTEN overexpression significantly inhibited TGFβ1‐ or unilateral ureteral obstruction (UUO)‐induced FAK signaling pathway activation both in vitro and in vivo; more importantly, PTEN silence enhanced TGFβ1‐ or UUO‐induced fibrosis, while FAK inhibitor PF567721 significantly reversed the effects of PTEN silence, indicating that PTEN exerted its effects on TGFβ1‐ and UUO‐induced fibrotic development in vitro and in vivo via inhibiting FAK signaling pathway. In summary, these findings indicate that PTEN could improve cellular fibrotic changes and renal fibrosis via inhibiting FAK/AKT signaling pathway. Restoring PTEN expression to target FAK/AKT signaling pathway might be a potent strategy for renal fibrosis treatment.

3DVT is a feasible and useful preoperative assessment method in patients undergoing laparoscopic surgery for PHEO/PGL. This imaging technique accurately shows the relationship between the tumor and peripheral structures and aids the surgeon's understanding of the anatomic structure in the operative area and in surgical planning.