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Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo.
Diabetes Res Clin Pract. 2014 Aug; 105(2):206-16.DR

Abstract

AIM

Inflammation and extracellular matrix hyperplasia are crucial in the pathogenesis of tubulointerstitial fibrosis (TIF) involved in diabetic nephropathy (DN). Macrophage accumulation plays a major role, but whether immune factors contribute to DN pathogenesis is not well understood. This study aimed to investigate TLR4-MyD88-NF-κB-dependent pathway's involvement in TIF pathogenesis.

METHODS

STZ-induced diabetic rats and rat renal tubular epithelial NRK-52E cells cultured under high glucose conditions were used as in vivo and in vitro models, respectively. Real-time RT-PCR, western blot, immunohistochemistry and immunofluorescence were performed to examine the mRNA and protein levels of TLR4, MyD88, NF-κB, MCP-1, and α-SMA.

RESULTS

Compared with 5.5 mmol/L glucose, treatment of NRK-52E cells with 25 and 50 mmol/L d-glucose resulted in significantly increased TLR4 and MyD88 mRNA and protein levels (P<0.05). TLR4 and MyD88 were detected in the cytoplasm of most NRK-52E cells cultured under high glucose. Pronounced damage in the renal tubulointerstitium was observed in diabetic rats (scores: 3.82 ± 0.65 vs. 0.38 ± 0.08, P<0.01). Compared with the normal controls, a sharp upregulation of TLR4, MyD88, NF-κB p65, MCP-1, and α-SMA mRNA and protein levels was observed in diabetic rat kidneys (P<0.05). In diabetic animals, TLR4 and MyD88 were strongly expressed in the cytoplasm, while NF-κB p65 was widely expressed in cytoplasm and nuclei of renal tubular epithelial cells.

CONCLUSION

The inflammatory reaction and epithelial-mesenchymal transformation observed in renal tubulointerstitium may be the result of overactivation of the TLR4-MyD88-NF-κB-dependent innate immunity under high glucose, and may be involved in DN occurrence and progression.

Authors+Show Affiliations

Department of endocrinology, General hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Province, China.Department of endocrinology, General hospital of Tianjin Medical University, Tianjin 300052, China.Department of endocrinology, General hospital of Tianjin Medical University, Tianjin 300052, China.Cardiovascular and Cerebrovascular Disease Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Province, China. Electronic address: helanjie@medmail.com.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24894085

Citation

Liu, Ping, et al. "Expression and Cellular Distribution of TLR4, MyD88, and NF-κB in Diabetic Renal Tubulointerstitial Fibrosis, in Vitro and in Vivo." Diabetes Research and Clinical Practice, vol. 105, no. 2, 2014, pp. 206-16.
Liu P, Li F, Qiu M, et al. Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo. Diabetes Res Clin Pract. 2014;105(2):206-16.
Liu, P., Li, F., Qiu, M., & He, L. (2014). Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo. Diabetes Research and Clinical Practice, 105(2), 206-16. https://doi.org/10.1016/j.diabres.2014.04.020
Liu P, et al. Expression and Cellular Distribution of TLR4, MyD88, and NF-κB in Diabetic Renal Tubulointerstitial Fibrosis, in Vitro and in Vivo. Diabetes Res Clin Pract. 2014;105(2):206-16. PubMed PMID: 24894085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo. AU - Liu,Ping, AU - Li,Feng'ao, AU - Qiu,Mingcai, AU - He,Lanjie, Y1 - 2014/04/28/ PY - 2013/12/23/received PY - 2014/03/20/revised PY - 2014/04/19/accepted PY - 2014/6/5/entrez PY - 2014/6/5/pubmed PY - 2014/11/14/medline KW - Diabetic nephropathy KW - MyD88 KW - NF-κB KW - Renal tubulointerstitial fibrosis KW - TLR4 SP - 206 EP - 16 JF - Diabetes research and clinical practice JO - Diabetes Res Clin Pract VL - 105 IS - 2 N2 - AIM: Inflammation and extracellular matrix hyperplasia are crucial in the pathogenesis of tubulointerstitial fibrosis (TIF) involved in diabetic nephropathy (DN). Macrophage accumulation plays a major role, but whether immune factors contribute to DN pathogenesis is not well understood. This study aimed to investigate TLR4-MyD88-NF-κB-dependent pathway's involvement in TIF pathogenesis. METHODS: STZ-induced diabetic rats and rat renal tubular epithelial NRK-52E cells cultured under high glucose conditions were used as in vivo and in vitro models, respectively. Real-time RT-PCR, western blot, immunohistochemistry and immunofluorescence were performed to examine the mRNA and protein levels of TLR4, MyD88, NF-κB, MCP-1, and α-SMA. RESULTS: Compared with 5.5 mmol/L glucose, treatment of NRK-52E cells with 25 and 50 mmol/L d-glucose resulted in significantly increased TLR4 and MyD88 mRNA and protein levels (P<0.05). TLR4 and MyD88 were detected in the cytoplasm of most NRK-52E cells cultured under high glucose. Pronounced damage in the renal tubulointerstitium was observed in diabetic rats (scores: 3.82 ± 0.65 vs. 0.38 ± 0.08, P<0.01). Compared with the normal controls, a sharp upregulation of TLR4, MyD88, NF-κB p65, MCP-1, and α-SMA mRNA and protein levels was observed in diabetic rat kidneys (P<0.05). In diabetic animals, TLR4 and MyD88 were strongly expressed in the cytoplasm, while NF-κB p65 was widely expressed in cytoplasm and nuclei of renal tubular epithelial cells. CONCLUSION: The inflammatory reaction and epithelial-mesenchymal transformation observed in renal tubulointerstitium may be the result of overactivation of the TLR4-MyD88-NF-κB-dependent innate immunity under high glucose, and may be involved in DN occurrence and progression. SN - 1872-8227 UR - https://www.unboundmedicine.com/medline/citation/24894085/Expression_and_cellular_distribution_of_TLR4_MyD88_and_NF_κB_in_diabetic_renal_tubulointerstitial_fibrosis_in_vitro_and_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8227(14)00203-4 DB - PRIME DP - Unbound Medicine ER -