Heilongjiang Province Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, No. 3, Tongxiang Street, Aimin District, 157011, Mudanjiang, Heilongjiang, China.
College of Life Sciences, Mudanjiang Medical University, 157011, Mudanjiang, Heilongjiang, China.
Mol Med. 2024 Apr 19;30(1):52. doi: 10.1186/s10020-024-00815-w.
Skin fibrosis affects the normal function of the skin. TGF-β1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-β1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-β1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE.
The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-β1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics.
SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis.
F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.
皮肤纤维化会影响皮肤的正常功能。TGF-β1 是影响器官纤维化的关键细胞因子，潜伏相关肽（LAP）是 TGF-β1 激活所必需的。我们之前构建并制备了截断的 LAP（tLAP），并证实 tLAP 通过影响 TGF-β1 抑制肝纤维化。SPACE 肽具有透皮和跨膜功能。SPACE 促进大分子通过角质层进入真皮的传递。本研究旨在通过 SPACE 递送来缓解皮肤纤维化。
构建了 SPACE-tLAP（SE-tLAP）重组质粒。通过镍亲和层析纯化 SE-tLAP。评估 SE-tLAP 对 TGF-β1 诱导的 NIH-3T3 细胞增殖、迁移和纤维化相关及炎症因子表达的影响。使用 F127 作为载体构建 F127-SE-tLAP 水凝胶，以装载 SE-tLAP 多肽。评估 F127-SE-tLAP 的降解、药物释放和生物相容性。使用博来霉素诱导小鼠皮肤纤维化。用 HE、Masson 和免疫组织化学观察皮肤组织学特征。
SE-tLAP 抑制了 NIH-3T3 细胞中纤维化相关和炎症因子的增殖、迁移和表达。F127-SE-tLAP 显著减少 ECM 的产生、胶原沉积和纤维化的病理变化，从而缓解皮肤纤维化。
F127-SE-tLAP 可以增加 LAP 的透皮传递，减少 ECM 的产生和沉积，抑制真皮胶原纤维的形成，从而缓解皮肤纤维化的进展。它可能为皮肤纤维化的治疗提供新的思路。
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