Endogenously produced LG3/4/5-peptide protects testes against toxicant-induced injury
| Autor: | Siwen Wu, C. Yan Cheng, Linxi Li, Ren-Shan Ge, Huitao Li, Baiping Mao, Lixiu Lv |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research Immunology Drug development Transfection Article Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience Protein Domains In vivo Testis medicine Animals lcsh:QH573-671 Cell proliferation Actin Sertoli Cells 030102 biochemistry & molecular biology lcsh:Cytology Chemistry Cell growth Biological activity Cell Biology Sertoli cell Peptide Fragments In vitro Rats Cell biology 030104 developmental biology medicine.anatomical_structure Laminin Spermatogenesis |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 6, Pp 1-19 (2020) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2608-8 |
| Popis: | Laminin-α2 chain is one of the major constituent proteins of the basement membrane in the mammalian testis. The laminin-type globular (LG) domains of LG3, 4 and 5 (LG3/4/5, an 80 kDa fragment) can be cleaved from laminin-α2 chain at the C-terminus via the action of matrix metalloproteinase 9 (MMP-9). This LG3/4/5 is a biologically active fragment, capable of modulating the Sertoli cell blood–testis barrier (BTB) function by tightening the barrier both in vitro and in vivo. Overexpression of LG3/4/5 cloned into a mammalian expression vector pCI-neo in Sertoli cells in a Sertoli cell in vitro model with a functional BTB also protected Sertoli cells from cadmium chloride (CdCl2, an environmental toxicant) mediated cell injury. Importantly, overexpression of LG3/4/5 in the testis in vivo was found to block or rescue cadmium-induced BTB disruption and testis injury. LG3/4/5 was found to exert its BTB and spermatogenesis promoting effects through corrective spatiotemporal expression of actin- and MT-based regulatory proteins by maintaining the cytoskeletons in the testis, illustrating the therapeutic implication of this novel bioactive fragment. |
| Databáze: | OpenAIRE |
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