Endogenously produced LG3/4/5-peptide protects testes against toxicant-induced injury

• Published in: Cell death & disease Vol. 11; no. 6; p. 436
• Main Authors: Li, Linxi, Mao, Baiping, Wu, Siwen, Li, Huitao, Lv, Lixiu, Ge, Renshan, Cheng, C. Yan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-06-2020; Springer Nature B.V
• Subjects: 38; 38/109; 631/136/2091; 64; 692/308/153; Actin; Animals; Antibodies; Biochemistry; Biological activity; Biomedical and Life Sciences; C-Terminus; Cadmium; Cadmium chloride; Cell Biology; Cell Culture; Cell injury; Cell Proliferation; Gelatinase B; Immunology; Laminin; Laminin - metabolism; Life Sciences; Male; Matrix metalloproteinase; Metalloproteinase; Peptide Fragments - metabolism; Protein Domains; Rats; Rats, Sprague-Dawley; Regulatory proteins; Sertoli cells; Sertoli Cells - metabolism; Spermatogenesis; Testes; Testis - drug effects; Toxicants; Transfection
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2608-8

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 (CdCl
2
, 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.