Page 121 - CSIR-IGIB Annual Report 2020-21
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Combined metabolome and proteome profiling Analysis of Curcuma Longa miRNA
Rheumatoid Arthritis (RA) is a chronic, The discovery of plant miRNAs and their roles in
autoimmune disease and is still unclear and the biology of mammalian cells and animal organs
remains challenging. Current trends in represents the first evidence of cross-kingdom
metabolomics analysis and discoveries have transfer of functionally active miRNAs and thus
revealed distinctive features of metabolites. opens a new avenue to explore miRNA-mediated
Therefore, understanding effects of the unique animal plant interactions. Therefore, this
and/or differential metabolites on RA will be proposed study attempts to cover the gap and
useful in evaluating inflammatory response and underlines the necessity of further studies
aggressive phenotype of RA-FLS in relation to between plant exogenous genetic material
differential proteome analysis. Metabolomic controlling mammalian gene expressions
along with proteomics is the new omics which will providing therapeutic applications. This project
be used to reveal metabolites and proteins profile aims to explore the potential of herbal plant
to discriminate a disease from non-disease miRNA in cross-kingdom communication.
condition. It may help to introduce new disease Achievement Blood samples were collected from
defining marker proteins and metabolites for RA confirmed RA patients (n=4) at the age group of
assessment. All participants screened based on 23-45 years. Similarly, blood of healthy control
Rheumatoid factor (RF) titre and Anti-cyclic (HC, n=5) samples with no history of joint
citrullinated peptide antibody (ACCPA) levels. All symptoms or arthritic relative diseases was also
RA samples with positive RF factor and ACPA collected. To study the anti-inflammatory effect of
values of RA (n=33) and healthy (n=5) were clo-miR-14 in primary RA cells, cells were isolated
calculated. The total 12 samples were taken for from synovial tissues and transfected with clo-
metabolomic analysis via HPLC/LCMS. Total miR-14. Impact of this transfection on expression
altered 3430 m/z were found in RA and controls of pro-inflammatory genes was studied. Forty-
(Log2 fold change > ±1, p < 0.05). Total 123 m/z are eight hours post transfections, a significant down-
found to be significantly regulated in disease regulation of the p65 subunit of NF-kB was
condition: 72 were upregulated and 51 observed in clo-miR-14 transfected cells. In the
downregulated. Significant metabolites fall under future, we will evaluate the levels of clo-miR-14 in
the sphingolipid and glycerophospholipid the sera samples. Transfection of C. longa miRNA
metabolism pathway. together with clo-miR-14 in RA primary cells with
targeted protein expression of the respective
Identification of disease-specific proteome and genes will be attempted in future. We aim to
metabolome are the new trending omics which identify possible stable carrier for transferring
can be used to reveal proteins and metabolites xeno-miRNA clo-mir-14 to RA primary cells. We
profile globally that will help us to decipher the will screen targeted mRNAs effected by in vitro
more prominent metabolite/protein or transfection of clo-mir-14 in primary cells of RA. In
association as marker. The proposed work will vivo studies will be performed in model systems
provide disease-associated metabolites and (CIA) for inflammatory protein expression after
altered proteins that may specify the disease. transfecting with clo-mir- 4. Based on this study
Revealing the disease specific marker will provide oral delivery of synthetic oligonucleotides can be
a target to develop a diagnostic tool at an early developed in the near future for providing relief
stage of RA to initiate treatment. Metabolomics from chronic inflammation of RA.
and proteomic analysis will provide baseline
profiles for future investigation of RA disease Early detection of Osteoarthritis
specific proteins and their relationship to Osteoarthritis (OA) is a chronic wear and tear
circulating metabolites. disease of joints which occurs at older age. The
absence of biological markers makes OA difficult
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