Expression of nerve growth factor is upregulated in the rat thymic epithelial cells during thymus regeneration following acute thymic involution

Lee, Hae Young; Kim, Sung-Min; Shim, Na-Ri; Bae, Soo-Kyung; Jung, Il-Gun; Kwak, Jong‐Young; Kim, Bong-Seon; Kim, Jae-Bong; Moon, Joonho; Chung, Joo-Seop; Yoon, Sik

doi:10.1016/j.regpep.2006.12.015

Cited by 18 publications

(19 citation statements)

References 36 publications

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“…The mice were used at 8-10 weeks of age and they were given a single intraperitoneal dose of CY (450 mg/kg, Sigma) as described in previous studies (Yoon et al, 1997(Yoon et al, , 2003Lee et al, 2005Lee et al, , 2007. The animals were given RANKL intraperitoneally at a dose of 10 µg per mice.…”

Section: Animals Experimental Thymic Regeneration Model and In Vivomentioning

confidence: 99%

“…It has been well documented that acute thymic involution induced in experimental animals is followed by intensive regeneration after removal of the causative stimuli (Milicevic et al, 1984;Yoon et al, 1997Yoon et al, , 2003Lee et al, 2005Lee et al, , 2007. Cyclophosphamide (CY) exhibits a selective suppressive action on various populations and subpopula-tions of lymphoid cells (Turk and Poulter, 1972;Ozer et al, 1982;Zhu et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

“…Cyclophosphamide (CY) exhibits a selective suppressive action on various populations and subpopula-tions of lymphoid cells (Turk and Poulter, 1972;Ozer et al, 1982;Zhu et al, 1987). Thus, the application of CY represents a long-established method to induce thymic involution and investigate thymic regeneration (Milicevic et al, 1984;Yoon et al, 1997Yoon et al, , 2003Milicevic and Milicevic, 2004;Lee et al, 2005Lee et al, , 2007. Moreover, CY as well as a number of other agents that induce the acute thymic involution, can be successfully used not only to study the process of regeneration, but also to shed light on the normal thymocytopoiesis, because the changes that occur during the former always mirror the latter process and enable its better understanding (Milicevic and Milicevic, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, CY as well as a number of other agents that induce the acute thymic involution, can be successfully used not only to study the process of regeneration, but also to shed light on the normal thymocytopoiesis, because the changes that occur during the former always mirror the latter process and enable its better understanding (Milicevic and Milicevic, 2004). Of importance, it has been suggested that thymic epithelial cells may play a critical role in thymic regeneration (Milicevic et al, 1984;Yoon et al, 1997Yoon et al, , 2003Milicevic and Milicevic, 2004;Lee et al, , 2007. However, the molecular mechanisms underlying thymus regeneration are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

Lee

Park

et al. 2008

Exp Mol Med

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In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-κB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.

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Section: Animals Experimental Thymic Regeneration Model and In Vivomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

Lee

Park

et al. 2008

Exp Mol Med

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“…They were allowed to adjust to their environment for 1 week, and were used at 8-10 weeks of age. Since cyclophosphamide, a DNA alkylating agent commonly used in chemotherapy, is a long-established method of investigating thymic regeneration (Milicévić et al, 1984;Yoon et al, 1997Yoon et al, , 2003Lee et al, 2005Lee et al, , 2007Lee et al, , 2008a, the animals were given a single intraperitoneal dose of cyclophosphamide (400 mg/kg body weight, Sigma) in normal saline, and were killed in groups of four or more at 1, 2, 3, 4, 5, 6, 7 and 10 days after injection. Mice given the same amount of normal saline were used as controls.…”

Section: Experimental Model Of Acute Thymic Involution and Regenerationmentioning

confidence: 99%

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

Kim

et al. 2009

Exp Mol Med

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CD8+ DP and the intermediate thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in thymocytes during thymus regeneration. We also found that the interaction of 4-1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated with positive selection during recovery from acute thymic involution.

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Stimulatory effect of HGF‐overexpressing adipose tissue‐derived mesenchymal stem cells on thymus regeneration in a rat thymus involution model

Jung

Han

Kim

et al. 2014

Cell Biology International

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The thymus is the central lymphoid organ providing a unique and essential microenvironment for T-cell precursor development into mature functionally competent T-lymphocytes. Thus, it is important to develop the strategies for enhancing thymic regeneration from involution induced by a variety of clinical treatments and conditions. Hepatocyte growth factor (HGF) promotes proliferation in a variety of cell types. We have used stem cell-based HGF gene therapy to enhance regeneration from acute thymic involution. HGF-overexpressing human adipose tissue-derived mesenchymal stem cells (HGF-hATMSCs) were generated by liposomal transfection with the pMEX expression vector, constructed by inserting the HGF gene. Significantly increased HGF expression in these cells was confirmed by reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay. HGF produced by HGF-hATMSCs enhanced the proliferation of a mouse thymic epithelial cell line and the expression of interleukin-7 in vitro. We also examined the effect of HGF-hATMSCs on thymic regeneration in rats with acute thymic involution. Significant increases in thymus size and weight, as well as the number of thymocytes (especially, early thymocyte progenitors), were seen in the HGF-hATMSCs-treated rats compared to saline-treated control animals. A stimulatory effect of HGF-hATMSCs on thymic regeneration has therefore been shown, highlighting the clinical value of HGF-hATMSCs for treating thymic involution.

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Expression of nerve growth factor is upregulated in the rat thymic epithelial cells during thymus regeneration following acute thymic involution

Cited by 18 publications

References 36 publications

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

Stimulatory effect of HGF‐overexpressing adipose tissue‐derived mesenchymal stem cells on thymus regeneration in a rat thymus involution model

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