AUTHOR=Yin Xin , Zhao Yan , Zheng Yi Li , Wang Jin Zhi , Li Wei , Lu Qiu Ju , Huang Qiang Nian , Zhang Chen Yu , Chen Xi , Ma Ji Zheng 

TITLE=Time-Course Responses of Muscle-Specific MicroRNAs Following Acute Uphill or Downhill Exercise in Sprague-Dawley Rats

JOURNAL=Frontiers in Physiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.01275

DOI=10.3389/fphys.2019.01275

ISSN=1664-042X

ABSTRACT=<p><bold>Objective:</bold> The physiological characteristics and acute responses underpinning uphill running differ from those of downhill running and remain less understood. This study aimed to evaluate time-course changes of muscle-specific microRNA (miRNA) responses in striated muscle or circulation in response to uphill and downhill running.</p><p><bold>Methods:</bold> Male Sprague-Dawley rats (<italic>n</italic> = 84) were randomly assigned to a sedentary group (<italic>n</italic> = 12) and an exercise group (<italic>n</italic> = 72). The exercise group performed 90 min of uphill or downhill running. The striated muscle (quadriceps, gastrocnemius, soleus, and cardiac muscle) or circulation (plasma, exosome, exosome-free) levels of six muscle-specific miRNAs (miR-1, miR-133a, miR-133b, miR-206, miR-208a, and miR-499) were assessed at rest, immediately following exercise, and during recovery (1 h and 48 h).</p><p><bold>Results:</bold> Our results show that miR-1 and miR-133a levels are both decreased in quadriceps following downhill running (<italic>p</italic> &lt; 0.05) while there is no change after uphill running (<italic>p</italic> &gt; 0.05). In gastrocnemius, both uphill and downhill running decreased miR-1 level immediately after exercise and returned to baseline during recovery (<italic>p</italic> &lt; 0.05): interestingly, only miR-499 significantly increased following uphill running (<italic>p</italic> &gt; 0.05). Of the cell-free miRNAs in circulation, only the miR-133b levels in plasma were not affected following uphill running (<italic>p</italic> &gt; 0.05); the other miRNA levels significantly increased immediately after exercise (<italic>p</italic> &lt; 0.05), decreased at 1 h and significantly increased at 48 h after exercise (<italic>p</italic> &lt; 0.05). All selected miRNA levels in exosomes were not affected following uphill running (<italic>p</italic> &gt; 0.05), while all selected miRNA levels significantly increased during early recovery after downhill running (<italic>p</italic> &gt; 0.05). In addition, only the miR-133a level in the exosome-free condition showed significant changes following uphill running (<italic>p</italic> &lt; 0.05), while miR-1, miR-133a, and miR-499 levels showed significant changes after downhill running (<italic>p</italic> &lt; 0.05).</p><p><bold>Conclusion:</bold> The results indicate that miRNA undergoes dynamic changes in tissue may play an important role in regulating different stress/adaptation following uphill and downhill running. It is likely that changed miRNA levels in plasma may act as a new biomarker for monitoring whole muscular stress during recovery.</p>