THE ROLE OF RNASE L IN THE KIDNEY FUNCTION
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Cleveland State University / OhioLINK
2019
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=csu1557424763775669 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-csu15574247637756692021-08-03T07:11:12Z THE ROLE OF RNASE L IN THE KIDNEY FUNCTION Alghamdi, Norah Chemistry Immunology Analytical Chemistry Anatomy and Physiology Animal Sciences Animals Biochemistry Biology Biomedical Research Cellular Biology RNase L kidney folic acid acute kidney injury creatinine EGF ADAM10 AKI Renal diseases are a prevalent problem. The data released by the US Renal Data System show increasing of the incidence in acute kidney injury (AKI) at a rate of 14 % since 2001. AKI severity results in patient morbidity and mortality. Studies in the animal model of AKI reveal that epidermal growth factor (EGF) enhances recovery of renal function and structure after AKI by activating its receptor (EGF) that promotes renal tubular cell proliferation. However, it has been also reported that EGF/EGFR activation contributes to the development and progression of renal diseases such as obstructive nephropathy, diabetic nephropathy, hypertensive nephropathy, and glomerulonephritis through mechanisms involved in induction of tubular atrophy, overproduction of inflammatory factors, and/or promotion of glomerular and vascular injury. 2-5A dependent RNase L (RNase L) is an interferon (IFN)-inducible enzyme that plays an important role in the molecular mechanisms of IFN against viral and microbial infection. Studies have shown that RNase L has diverse and critical cellular functions, including cell differentiation, proliferation, senescence and apoptosis, autophagy, tumorigenesis, and the control of the innate immune response. By using RNase L knockout mice, we found that the absence of RNase L enhances kidney recovery from AKI. The lack of RNase L exclusively blocks EGF excretion from the kidney into urine. Mechanistic study revealed that A Disinterring and metalloproteinase (ADAM10), the enzyme responsible of EGF cleavage in kidney, is down regulated in the kidney of RNase L deficient mice. Interestingly, activation of EGFR which enhances kidney recovery after AKI was observed in RNase L deficient mice. Moreover, the level of serum creatinine, an important biomarker to assess kidney function, was significantly decreased in RNase L null mice. This study suggests that RNase L may play an important role in the kidney function, which is a novel target for treating kidney disorders such as AKI. Our findings suggest that RNase L may play an important role in kidney recovery from AKI by activating the EGF/EGFR/AKT signaling pathway. 2019-05-10 English text Cleveland State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=csu1557424763775669 http://rave.ohiolink.edu/etdc/view?acc_num=csu1557424763775669 restricted--full text not available online This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Chemistry Immunology Analytical Chemistry Anatomy and Physiology Animal Sciences Animals Biochemistry Biology Biomedical Research Cellular Biology RNase L kidney folic acid acute kidney injury creatinine EGF ADAM10 AKI |
| spellingShingle |
Chemistry Immunology Analytical Chemistry Anatomy and Physiology Animal Sciences Animals Biochemistry Biology Biomedical Research Cellular Biology RNase L kidney folic acid acute kidney injury creatinine EGF ADAM10 AKI Alghamdi, Norah THE ROLE OF RNASE L IN THE KIDNEY FUNCTION |
| author |
Alghamdi, Norah |
| author_facet |
Alghamdi, Norah |
| author_sort |
Alghamdi, Norah |
| title |
THE ROLE OF RNASE L IN THE KIDNEY FUNCTION |
| title_short |
THE ROLE OF RNASE L IN THE KIDNEY FUNCTION |
| title_full |
THE ROLE OF RNASE L IN THE KIDNEY FUNCTION |
| title_fullStr |
THE ROLE OF RNASE L IN THE KIDNEY FUNCTION |
| title_full_unstemmed |
THE ROLE OF RNASE L IN THE KIDNEY FUNCTION |
| title_sort |
role of rnase l in the kidney function |
| publisher |
Cleveland State University / OhioLINK |
| publishDate |
2019 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=csu1557424763775669 |
| work_keys_str_mv |
AT alghamdinorah theroleofrnaselinthekidneyfunction AT alghamdinorah roleofrnaselinthekidneyfunction |
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1719455613977624576 |