Regulation of granulosa cell functions through NRP-1 mediated internalization of follicular fluid non-exosomal miR-210


Posted: 2021-10-02 19:00:00
Cell Tissue Res . 2021 Oct 2. doi: 10.1007/s00441-021-03524-6. Online ahead of print. Affiliations Expand Affiliations 1 Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal, 132001, Haryana, India. 2 Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal, 132001, Haryana, India. drdheer.singh@gmail.com. Item in Clipboard Suman Kumari et al. Cell Tissue Res. 2021. Show details Display options Display options Format Cell Tissue Res . 2021 Oct 2. doi: 10.1007/s00441-021-03524-6. Online ahead of print. Affiliations 1 Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal, 132001, Haryana, India. 2 Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal, 132001, Haryana, India. drdheer.singh@gmail.com. Item in Clipboard CiteDisplay options Display options Format Abstract Crosstalk between follicular fluid (FF) and granulosa cells (GCs) plays a vital role in the regulation of folliculogenesis, ensuring regular reproductive cycle in mammals. This crosstalk is primarily mediated by hormones and signaling molecules, such as cytokines and chemokines. Recently, extracellular microRNAs (miRNAs) have gained a lot of attention in cell-to-cell communication. Extracellular miRNA transportation occurs through exosomes, a kind of micro-vesicles produced from almost all cells. However, the mode of non-exosomal miRNA internalization is not much studied. In the present study, we explored the role of neuropilin-1 (NRP-1) as a receptor in internalizing FF non-exosomal miRNAs in GCs. We first confirmed the expression of NRP-1 in GCs during follicular development followed by its role in the internalization of miR-210, a non-exosomal miRNA. This study showed that incubation of GCs with a non-exosomal fraction of FF increased the content of miR-210 in GCs as compared to their control. To illustrate the role of NRP-1 as a receptor, NRP-1 was knockdown using siRNA. Silencing experimental results showed a significant decrease in uptake of miR-210 in NRP-1 knockdown GCs. Furthermore, downstream expression analysis of miR-210 target genes (CYP19A1, PCNA, and EFNA3) also confirmed the NRP-1 mediated miR-210 internalization. Results of the present study clearly demonstrated that FF non-exosomal miR-210 can be internalized through the NRP-1 receptor. Furthermore, differential expression of NRP-1 in GCs suggests its role in follicular development. Overall, these findings suggest that FF non-exosomal miRNA plays an important role in GC functions and female reproduction. Keywords: Follicular fluid; Granulosa cells; NRP-1; Non-exosomal fraction; miR-210; miRNA internalization. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. References Arif M, Pandey R, Alam P, Jiang S, Sadayappan S, Paul A, Ahmed RP (2017) MicroRNA-210-mediated proliferation, survival, and angiogenesis promote cardiac repair post myocardial infarction in rodents. J Mol Med 95:1369–1385 - DOI Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, Tait JF (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci 108:5003–5008 - DOI Biswas S, Roy S, Banerjee J, Hussain SRA, Khanna S, Meenakshisundaram G, Kuppusamy P, Friedman A, Sen CK (2010) Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds. Proc Natl Acad Sci 107:6976–6981 - DOI Bruder D, Probst-Kepper M, Westendorf AM, Geffers R, Beissert S, Loser K, von Boehmer H, BuerJ HW (2004) Frontline: Neuropilin-1: a surface marker of regulatory T cells. Eur J Immunol 34:623–630 - DOI Buensuceso AV, Deroo BJ (2013) The ephrin signaling pathway regulates morphology and adhesion of mouse granulosa cells in vitro. Biol Reprod 88:25–1 Show all 46 references LinkOut - more resources Research MaterialsMiscellaneous [x] Cite Copy Format: Send To [x]

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脂肪組織がCOVID-19の悪化に重要な役割を果たすという仮説

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