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Expression of transforming growth factor-beta1 limits renal ischemia-reperfusion injury.
Transplantation. 2010 Jun 15; 89(11):1320-7.T

Abstract

BACKGROUND

Renal ischemia-reperfusion injury (IRI) largely contributes to kidney transplant dysfunction and acute kidney injury, but its pathogenesis is not fully understood. In this study, the role of transforming growth factor (TGF)-beta1 in renal IRI is investigated using TGF-beta1 deficient mice.

METHOD

Human renal tubular epithelial cells (TEC) line (HK-2) was used as an in vitro model, and cell apoptosis was determined by flow cytometric analysis. Renal IRI was induced in mice by clamping renal vein and artery for 45 min at 32 degrees C.

RESULTS

Here, we showed that in cultures of HK-2 cells, TGF-beta1 expression was up-regulated by tumor necrosis factor (TNF)-alpha. Neutralization of TGF-beta1 activity increased both spontaneous and TNF-alpha-mediated apoptosis, and knockdown of TGF-beta1 expression increased the sensitivity of cell apoptosis to TNF-alpha. In a mouse model of renal IRI, a deficiency in TGF-beta1 expression increased the severity of renal injury, as indicated by more severe renal tubular damage, higher levels of serum creatinine or blood urea nitrogen in TGF-beta1 deficient mice as compared with those in wild-type controls. Further experiments showed that the antiapoptosis of TGF-beta1 correlated with up-regulation of Bcl-2 in kidney cells.

CONCLUSION

Expression of TGF-beta1 in TECs, potentially induced by proinflammatory TNF-alpha, renders TECs resistance to cell death. In mice, TGF-beta1 deficiency results in more prone to IRI. These data imply that TGF-beta1 may act as a feedback survival factor in the resistance to kidney injury and maintenance of epithelium homeostasis.

Authors+Show Affiliations

Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20458271

Citation

Guan, Qiunong, et al. "Expression of Transforming Growth Factor-beta1 Limits Renal Ischemia-reperfusion Injury." Transplantation, vol. 89, no. 11, 2010, pp. 1320-7.
Guan Q, Nguan CY, Du C. Expression of transforming growth factor-beta1 limits renal ischemia-reperfusion injury. Transplantation. 2010;89(11):1320-7.
Guan, Q., Nguan, C. Y., & Du, C. (2010). Expression of transforming growth factor-beta1 limits renal ischemia-reperfusion injury. Transplantation, 89(11), 1320-7. https://doi.org/10.1097/TP.0b013e3181d8e9dc
Guan Q, Nguan CY, Du C. Expression of Transforming Growth Factor-beta1 Limits Renal Ischemia-reperfusion Injury. Transplantation. 2010 Jun 15;89(11):1320-7. PubMed PMID: 20458271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of transforming growth factor-beta1 limits renal ischemia-reperfusion injury. AU - Guan,Qiunong, AU - Nguan,Christopher Y C, AU - Du,Caigan, PY - 2010/5/12/entrez PY - 2010/5/12/pubmed PY - 2010/7/8/medline SP - 1320 EP - 7 JF - Transplantation JO - Transplantation VL - 89 IS - 11 N2 - BACKGROUND: Renal ischemia-reperfusion injury (IRI) largely contributes to kidney transplant dysfunction and acute kidney injury, but its pathogenesis is not fully understood. In this study, the role of transforming growth factor (TGF)-beta1 in renal IRI is investigated using TGF-beta1 deficient mice. METHOD: Human renal tubular epithelial cells (TEC) line (HK-2) was used as an in vitro model, and cell apoptosis was determined by flow cytometric analysis. Renal IRI was induced in mice by clamping renal vein and artery for 45 min at 32 degrees C. RESULTS: Here, we showed that in cultures of HK-2 cells, TGF-beta1 expression was up-regulated by tumor necrosis factor (TNF)-alpha. Neutralization of TGF-beta1 activity increased both spontaneous and TNF-alpha-mediated apoptosis, and knockdown of TGF-beta1 expression increased the sensitivity of cell apoptosis to TNF-alpha. In a mouse model of renal IRI, a deficiency in TGF-beta1 expression increased the severity of renal injury, as indicated by more severe renal tubular damage, higher levels of serum creatinine or blood urea nitrogen in TGF-beta1 deficient mice as compared with those in wild-type controls. Further experiments showed that the antiapoptosis of TGF-beta1 correlated with up-regulation of Bcl-2 in kidney cells. CONCLUSION: Expression of TGF-beta1 in TECs, potentially induced by proinflammatory TNF-alpha, renders TECs resistance to cell death. In mice, TGF-beta1 deficiency results in more prone to IRI. These data imply that TGF-beta1 may act as a feedback survival factor in the resistance to kidney injury and maintenance of epithelium homeostasis. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/20458271/Expression_of_transforming_growth_factor_beta1_limits_renal_ischemia_reperfusion_injury_ L2 - https://doi.org/10.1097/TP.0b013e3181d8e9dc DB - PRIME DP - Unbound Medicine ER -