Somatostatin (SST) is a regulatory peptide and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells. SST’s actions are mediated by a family of seven transmembrane domain G protein-coupled receptors that comprise five distinct subtypes (SSTR1-5). SSTR5 is one of the major SSTRs in the islets of Langerhans. Homeodomain-containing transcription factor pancreatic and duodenal homeobox-1 (PDX-1) is essential for pancreatic development, β cell differentiation, maintenance of normal β cell functions in adults and tumorigenesis. Recent studies show that SSTR5 acts as a negative regulator for PDX-1 expression and that SSTR5 mediates somatostatin’s inhibitory effect on cell proliferation and insulin expression/excretion through down-regulating PDX-1 expression. SSTR5 exerts its inhibitory effect on PDX-1 expression at both the transcriptional level by down-regulating PDX-1 mRNA and the post-translational level by enhancing PDX-1 ubiquitination. Identification of PDX-1 as a transcriptional target for SSTR5 may help in guiding the choice of therapeutic cancer treatments.
PKD is a founding member of CAMK group of kinases and there is ample evidence of its participation in important cellular process including stress. Due to the lack of specific inhibitors for its action in vivo, its protein targets are scarcely described. Even less is known about its role at regulating the transcription of target proteins. The miRNA are important regulators of protein expression and several groups are currently undertaking studies about its targets, enriching a database that will enable a better understanding of the networks in which they participate.
In this work we aimed to identify miRNA that are modulated by hyperosmotic stress in 3T3 expressing PKD‐1 cells as a means to understand the PKD participation in this cellular process.
We obtained the RNA from 3T3‐PKD‐1 cells and their control counterparts, without or with an hour challenge with 0.3M NaCl, and sought to identify the up‐ or down‐ regulated miRNA. This was performed using miRNA3.0 Affymetrix microchips, and analyzed with software provided.
We found that miRNA that are exclusively regulated by the PKD action after the 0.3M NaCl challenge are: mir‐103, mir135, which are down‐regulated, and mir27a, which is up‐regulated.
Some of the targets of the down regulated mir‐103 include Syntaxin‐17, which participates in the autophagosomes formation; inhibitory growth factor 5 which participates in proliferation; and cadherin‐11, which participates in shaping cell morphology. The mir‐135 has as targets complexin 1 that participates in vesicle transport. The up‐regulated mir‐27a has as targets the A2B adenosine receptors that help repair ischemia/reperfusion injury, the activin A receptor ‐type C and the Ubiquitin conjugating enzyme E2N and Polo‐like kinase that regulates the differentiation of various organs.
Grant Funding Source: IN222014
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