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MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA.
Am J Physiol Renal Physiol. 2020 Aug 01; 319(2):F202-F214.AJ

Abstract

Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-α gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-α by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis.

Authors+Show Affiliations

Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing, China.Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32628541

Citation

Su, Boxing, et al. "MiR-21 Promotes Calcium Oxalate-induced Renal Tubular Cell Injury By Targeting PPARA." American Journal of Physiology. Renal Physiology, vol. 319, no. 2, 2020, pp. F202-F214.
Su B, Han H, Ji C, et al. MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA. Am J Physiol Renal Physiol. 2020;319(2):F202-F214.
Su, B., Han, H., Ji, C., Hu, W., Yao, J., Yang, J., Fan, Y., & Li, J. (2020). MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA. American Journal of Physiology. Renal Physiology, 319(2), F202-F214. https://doi.org/10.1152/ajprenal.00132.2020
Su B, et al. MiR-21 Promotes Calcium Oxalate-induced Renal Tubular Cell Injury By Targeting PPARA. Am J Physiol Renal Physiol. 2020 Aug 1;319(2):F202-F214. PubMed PMID: 32628541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA. AU - Su,Boxing, AU - Han,Haibo, AU - Ji,Chaoyue, AU - Hu,Weiguo, AU - Yao,Jingjing, AU - Yang,Jianghui, AU - Fan,Yunfei, AU - Li,Jianxing, Y1 - 2020/07/06/ PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez KW - lipid metabolism KW - microRNA KW - peroxisome proliferator-activated receptor-α KW - renal injury SP - F202 EP - F214 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 319 IS - 2 N2 - Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-α gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-α by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/32628541/MiR-21_promotes_calcium_oxalate-induced_renal_tubular_cell_injury_by_targeting_PPARA L2 - https://journals.physiology.org/doi/10.1152/ajprenal.00132.2020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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