Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling
Muscle atrophy is a significant consequence of chronic kidney disease (CKD) that increases a patient’s risk of mortality and decrease their quality of life. In CKD patients, the circulation levels of FGF23 are significantly increased, but the exact pathological significance of the increase and relat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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The Korean Society of Nephrology
2012-06-01
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| Series: | Kidney Research and Clinical Practice |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211913212004688 |
| _version_ | 1818035415004741632 |
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| author | Shinsuke Kido Yui Hashimoto Hiroko Segawa Sawako Tatsumi Ken-ichi Miyamoto |
| author_facet | Shinsuke Kido Yui Hashimoto Hiroko Segawa Sawako Tatsumi Ken-ichi Miyamoto |
| author_sort | Shinsuke Kido |
| collection | DOAJ |
| description | Muscle atrophy is a significant consequence of chronic kidney disease (CKD) that increases a patient’s risk of mortality and decrease their quality of life. In CKD patients, the circulation levels of FGF23 are significantly increased, but the exact pathological significance of the increase and relationship between FGF23 and muscle atrophy are not clear. Because of Klohto, acts as a co-receptor of FGF23 is detectable in limited tissues including in kidney and brain, but not in skeletal muscles. In contrast, recently reports indicated that the extracellular domain of klohto is cleavage for some reason on the cell surface and detected in the blood in animals. In this study, we attempted to identify the causative factors responsible for the shedding of Klotho, and whether both FGF23 and Klohto induced muscle atrophy via reduction of insulin/IGF-I signaling. We first investigated by treating kidney cells with various factors related in pathological factors in CKD. As a result, we found that advanced glycation endproducts (AGEs), an accumulated in patients with CKD and diabetes mellitus, increases shedding of Klohto in kidney cells. It is common knowledge that insulin/IGF-I signaling is necessary for normal skeletal growth. As a result, we showed that both FGF23 and Klohto inhibited differentiation of cultured skeletal muscle cells through down-regulation of insulin/IGF-I signaling. These observations suggested a divergent role of FGF23 and soluble klohto in the regulation of skeletal muscle differentiation and thereby muscle atrophy under pathological conditioned in CKD patients. Our results further imply that FGF23/Klohto may serve a new therapeutic target for CKD-induced muscle atrophy. |
| first_indexed | 2024-12-10T06:54:41Z |
| format | Article |
| id | doaj.art-0a1cf0316f0d4273be66500093362f28 |
| institution | Directory Open Access Journal |
| issn | 2211-9132 |
| language | English |
| last_indexed | 2024-12-10T06:54:41Z |
| publishDate | 2012-06-01 |
| publisher | The Korean Society of Nephrology |
| record_format | Article |
| series | Kidney Research and Clinical Practice |
| spelling | doaj.art-0a1cf0316f0d4273be66500093362f282022-12-22T01:58:28ZengThe Korean Society of NephrologyKidney Research and Clinical Practice2211-91322012-06-01312A4410.1016/j.krcp.2012.04.435Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signalingShinsuke KidoYui HashimotoHiroko SegawaSawako TatsumiKen-ichi MiyamotoMuscle atrophy is a significant consequence of chronic kidney disease (CKD) that increases a patient’s risk of mortality and decrease their quality of life. In CKD patients, the circulation levels of FGF23 are significantly increased, but the exact pathological significance of the increase and relationship between FGF23 and muscle atrophy are not clear. Because of Klohto, acts as a co-receptor of FGF23 is detectable in limited tissues including in kidney and brain, but not in skeletal muscles. In contrast, recently reports indicated that the extracellular domain of klohto is cleavage for some reason on the cell surface and detected in the blood in animals. In this study, we attempted to identify the causative factors responsible for the shedding of Klotho, and whether both FGF23 and Klohto induced muscle atrophy via reduction of insulin/IGF-I signaling. We first investigated by treating kidney cells with various factors related in pathological factors in CKD. As a result, we found that advanced glycation endproducts (AGEs), an accumulated in patients with CKD and diabetes mellitus, increases shedding of Klohto in kidney cells. It is common knowledge that insulin/IGF-I signaling is necessary for normal skeletal growth. As a result, we showed that both FGF23 and Klohto inhibited differentiation of cultured skeletal muscle cells through down-regulation of insulin/IGF-I signaling. These observations suggested a divergent role of FGF23 and soluble klohto in the regulation of skeletal muscle differentiation and thereby muscle atrophy under pathological conditioned in CKD patients. Our results further imply that FGF23/Klohto may serve a new therapeutic target for CKD-induced muscle atrophy.http://www.sciencedirect.com/science/article/pii/S2211913212004688 |
| spellingShingle | Shinsuke Kido Yui Hashimoto Hiroko Segawa Sawako Tatsumi Ken-ichi Miyamoto Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling Kidney Research and Clinical Practice |
| title | Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling |
| title_full | Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling |
| title_fullStr | Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling |
| title_full_unstemmed | Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling |
| title_short | Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling |
| title_sort | muscle atrophy in patients wirh ckd results from fgf23 klotho mediated supression of insulin igf i signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2211913212004688 |
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