Impaired tissue regeneration corresponds with altered expression of developmental genes that persists in the metabolic memory state of diabetic zebrafish.
Impaired tissue regeneration corresponds with altered expression of developmental genes that persists in the metabolic memory state of diabetic zebrafish.
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DOI：
10.1111/wrr.12027
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Intine RV
中科院分区：
文献类型：
--
作者：
Sarras MP Jr;Leontovich AA;Olsen AS;Intine RV
正如我们实验室之前报道的，链脲佐菌素诱导的成年斑马鱼糖尿病（DM）会导致尾鳍再生监测的组织再生受损。链佐星停药后，会进入恢复阶段，通过胰腺 β 细胞再生来重新建立正常血糖。然而，与 DM 相关的鳍再生受损会在代谢记忆状态 (MM) 中无限期地持续，从而允许对 MM 的潜在机制进行后续分子分析。本研究的重点是阐明解释 DM 相关鳍再生受损的分子基础，以及为什么它持续进入 MM 状态，目的是更好地了解 MM。通过结合微阵列分析和生物信息学方法，我们的研究发现，在分析的 14,900 个转录本中，在 DM 鱼中发现了与组织发育和再生过程相关的 71 个基因的异常表达，并且这 71 个基因的表达改变在 MM 鱼中持续存在。在这 71 条鱼中鉴定出了主要发育和信号转导途径的关键调控基因。DM 状态下关键调控基因的异常表达持续到 MM 状态，为高血糖如何在成年斑马鱼 DM/MM 模型中诱导受损的鳍再生提供了合理的解释。
As previously reported by our lab streptozocin-induced Diabetes mellitus (DM) in adult zebrafish results in an impairment of tissue regeneration as monitored by caudal fin regeneration. Following streptozocin withdrawal, a recovery phase occurs to re-establish euglycemia, via pancreatic beta-cell regeneration. However, DM-associated impaired fin regeneration continues indefinitely in the metabolic memory state (MM) allowing for subsequent molecular analysis of the underlying mechanisms of MM. This study focuses on elucidating the molecular basis that explains the DM-associated impaired fin regeneration and why it persists into the MM state with the aim of better understanding MM. Using a combination of microarray analysis and bioinformatics approaches our study found that of the 14,900 transcripts analyzed, aberrant expression of 71 genes relating to tissue developmental and regeneration processes were identified in DM fish and the altered expression of these 71 genes persisted in MM fish. Key regulatory genes of major development, and signal transduction pathways were identified among this group of 71. The aberrant expression of key regulatory genes in the DM state that persist into the MM state provides a plausible explanation for how hyperglycemia induced impaired fin regeneration in the adult zebrafish DM/MM model.
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影响因子：
9.8
作者：
Brigstock, David R.
通讯作者：
Brigstock, David R.
DOI：
10.1073/pnas.87.1.404
发表时间：
1990-01-01
影响因子：
11.1
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作者：
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影响因子：
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作者：
Kowluru, RA
通讯作者：
Kowluru, RA