Tags

Type your tag names separated by a space and hit enter

miR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy.
Mol Cell Endocrinol. 2014 Jul 05; 392(1-2):163-72.MC

Abstract

Epithelial-to-mesenchymal transition (EMT) plays an important role in renal interstitial fibrosis (RIF) with diabetic nephropathy (DN). Smad7 (a inhibitory smad), a downstream signaling molecules of TGF-β1, represses the EMT. The physiological function of miR-21 is closely linked to EMT and RIF. However, it remained unclear whether miR-21 over-expression affected TGF-β1-induced EMT by regulating smad7 in DN. In this study, real-time RT-PCR, cell transfection, luciferase reporter gene assays, western blot and confocal microscope were used, respectively. Here, we found that miR-21 expression was upregulated by TGF-β1 in time- and concentration -dependent manner. Moreover, miR-21 over-expression enhanced TGF-β1-induced EMT(upregulation of a-SMA and downregulation of E-cadherin) by directly down-regulating smad7/p-smad7 and indirectly up-regulating smad3/p-smad3, accompanied by the decrease of Ccr and the increase of col-IV, FN, the content of collagen fibers, RTBM, RTIAW and ACR. Meantime, the siRNA experiment showed that smad7 can directly regulate a-SMA and E-cadherin expression. More importantly, miR-21 inhibitor can not only inhibit EMT and fibrosis but also ameliorate renal structure and function. In conclusion, our results demonstrated that miR-21 overexpression can contribute to TGF-β1-induced EMT by inhibiting target smad7, and that targeting miR-21 may be a better alternative to directly suppress TGF-β1-mediated fibrosis in DN.

Authors+Show Affiliations

Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China; Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Department of Endocrine and Metabolism, Capital Medical University, Beijing, China; Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China.Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China; Department of Endocrine and Metabolism, Capital Medical University, Beijing, China. Electronic address: gaoyb111@hotmail.com.Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China. Electronic address: jinkui.yang@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24887517

Citation

Wang, Jin-Yang, et al. "MiR-21 Overexpression Enhances TGF-β1-induced Epithelial-to-mesenchymal Transition By Target Smad7 and Aggravates Renal Damage in Diabetic Nephropathy." Molecular and Cellular Endocrinology, vol. 392, no. 1-2, 2014, pp. 163-72.
Wang JY, Gao YB, Zhang N, et al. MiR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy. Mol Cell Endocrinol. 2014;392(1-2):163-72.
Wang, J. Y., Gao, Y. B., Zhang, N., Zou, D. W., Wang, P., Zhu, Z. Y., Li, J. Y., Zhou, S. N., Wang, S. C., Wang, Y. Y., & Yang, J. K. (2014). MiR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy. Molecular and Cellular Endocrinology, 392(1-2), 163-72. https://doi.org/10.1016/j.mce.2014.05.018
Wang JY, et al. MiR-21 Overexpression Enhances TGF-β1-induced Epithelial-to-mesenchymal Transition By Target Smad7 and Aggravates Renal Damage in Diabetic Nephropathy. Mol Cell Endocrinol. 2014 Jul 5;392(1-2):163-72. PubMed PMID: 24887517.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy. AU - Wang,Jin-Yang, AU - Gao,Yan-Bin, AU - Zhang,Na, AU - Zou,Da-Wei, AU - Wang,Peng, AU - Zhu,Zhi-Yao, AU - Li,Jiao-Yang, AU - Zhou,Sheng-Nan, AU - Wang,Shao-Cheng, AU - Wang,Ying-Ying, AU - Yang,Jin-Kui, Y1 - 2014/06/02/ PY - 2014/01/14/received PY - 2014/04/24/revised PY - 2014/05/20/accepted PY - 2014/6/3/entrez PY - 2014/6/3/pubmed PY - 2015/2/20/medline KW - Diabetic nephropathy KW - Epithelial-to-mesenchymal transition KW - MicroRNA(miR) KW - Renal interstitial fibrosis KW - TGF-β1 SP - 163 EP - 72 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 392 IS - 1-2 N2 - Epithelial-to-mesenchymal transition (EMT) plays an important role in renal interstitial fibrosis (RIF) with diabetic nephropathy (DN). Smad7 (a inhibitory smad), a downstream signaling molecules of TGF-β1, represses the EMT. The physiological function of miR-21 is closely linked to EMT and RIF. However, it remained unclear whether miR-21 over-expression affected TGF-β1-induced EMT by regulating smad7 in DN. In this study, real-time RT-PCR, cell transfection, luciferase reporter gene assays, western blot and confocal microscope were used, respectively. Here, we found that miR-21 expression was upregulated by TGF-β1 in time- and concentration -dependent manner. Moreover, miR-21 over-expression enhanced TGF-β1-induced EMT(upregulation of a-SMA and downregulation of E-cadherin) by directly down-regulating smad7/p-smad7 and indirectly up-regulating smad3/p-smad3, accompanied by the decrease of Ccr and the increase of col-IV, FN, the content of collagen fibers, RTBM, RTIAW and ACR. Meantime, the siRNA experiment showed that smad7 can directly regulate a-SMA and E-cadherin expression. More importantly, miR-21 inhibitor can not only inhibit EMT and fibrosis but also ameliorate renal structure and function. In conclusion, our results demonstrated that miR-21 overexpression can contribute to TGF-β1-induced EMT by inhibiting target smad7, and that targeting miR-21 may be a better alternative to directly suppress TGF-β1-mediated fibrosis in DN. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/24887517/miR_21_overexpression_enhances_TGF_β1_induced_epithelial_to_mesenchymal_transition_by_target_smad7_and_aggravates_renal_damage_in_diabetic_nephropathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(14)00167-1 DB - PRIME DP - Unbound Medicine ER -