The Effect of ??-Melanocyte???Stimulating Hormone on Renal Tubular Cell Apoptosis and Tubulointerstitial Fibrosis in Cyclosporine A Nephrotoxicity

Lee, So Young; Jo, Sang Kyung; Cho, Won Yong; Kim, Hyoung Kyu; Won, Nam Hee

doi:10.1097/01.tp.0000144332.44435.ab

Cited by 35 publications

(27 citation statements)

References 32 publications

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“…Tubular cell apoptosis is also observed in animal [107][108][109] and cell culture models [110,111]. Cyclosporine-induced apoptosis is primarily triggered through the mitochondrial pathway.…”

Section: Typical Examples Of Apoptosis Induced By Nephrotoxic Agentsmentioning

confidence: 94%

Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation

et al. 2007

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Apoptosis plays a central role not only in the physiological processes of kidney growth and remodeling, but also in various human renal diseases and drug-induced nephrotoxicity. We present in a synthetic fashion the main molecular and cellular pathways leading to drug-induced apoptosis in kidney and the mechanisms regulating it. We illustrate them using three main nephrotoxic drugs (cisplatin, gentamicin, and cyclosporine A). We discuss the main regulators and effectors that have emerged as key targets for the design of therapeutic strategies. Novel approaches using gene therapy, antisense strategies, recombinant proteins, or compounds obtained from both classical organic and combinatorial chemistry are examined. Finally, key issues that need to be addressed for the success of apoptosis-based therapies are underlined.

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Section: Typical Examples Of Apoptosis Induced By Nephrotoxic Agentsmentioning

confidence: 94%

Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation

et al. 2007

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“…A recent report showed that collagen metabolism is a novel target of α-MSH [18]. It attenuated procollagen synthesis in experimental heart transplantation and reduced tubulointerstitial fibrosis in cyclosporine A (CsA)-induced nephrotoxicity [19,20]. Besides, α-MSH is known to increase collagenolytic activity by activating MMP-1 and MMP-2 [21,22].…”

Section: Introductionmentioning

confidence: 97%

α‐Melanocyte‐stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice

Lee

Jawan

Chou

et al. 2006

The Journal of Gene Medicine

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“…18 It attenuated procollagen synthesis in experimental heart transplantation and reduced tubulointerstitial fibrosis in cyclosporine A-induced nephrotoxicity. 19,20 Besides, a-MSH is known to increase collagenolytic activity by activating MMP-1 and MMP-2.…”

Section: Introductionmentioning

confidence: 99%

Electroporative α-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation

et al. 2006

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Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. a-Melanocyte-stimulating hormone (a-MSH) is a 13-amino-acid peptide with potent anti-inflammatory effects. We have previously demonstrated that a-MSH gene therapy protects against thioacetamide (TAA)-induced acute liver failure. Therefore, the aim of this study is to investigate whether a-MSH gene therapy possesses antihepatic fibrogenic effect. Liver fibrosis was induced by long-term TAA administration in mice. a-Melanocyte-stimulating hormone expression plasmid was delivered via electroporation after liver fibrosis was established. Our results showed that a-MSH gene therapy attenuated liver fibrosis in TAA-treated mice. Reverse transcription polymerase chain reaction revealed that a-MSH gene therapy attenuated the liver transforming growth factor-b1, collagen a1 and cell adhesion molecule mRNA upregulation. Following gene transfer, the expression of a-smooth muscle actin and cyclooxygenase-2 were both significantly attenuated. Further, a-MSH significantly increased matrix metalloproteinase (MMP), while tissue inhibitors of matrix metalloproteinase (TIMPs) were inactivated. In summary, a-MSH gene therapy reversed established liver fibrosis in mice and prevented the upregulated fibrogenic and pro-inflammatory gene responses after TAA administration. Its collagenolytic effect might be attributed to MMP and TIMP modulation. Hence, a-MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.

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The Effect of ??-Melanocyte???Stimulating Hormone on Renal Tubular Cell Apoptosis and Tubulointerstitial Fibrosis in Cyclosporine A Nephrotoxicity

Abstract: These findings suggest that chronic CsA nephrotoxicity is related to Bax and Bcl2-related apoptosis pathways, and that alpha-MSH can attenuate the CsA-induced tubulointerstitial fibrosis as well as tubular cell apoptosis.

Cited by 35 publications

References 32 publications

Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation

Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation

α‐Melanocyte‐stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice

Electroporative α-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation

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