SRI-011381 hydrochloride is an orally active activator of the transforming growth factor β (TGF-β) signaling pathway with neuroprotective effects[1]. TGF-β is a multi-effect cytokine that regulates cell growth and differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis, and cellular immune responses[2]. SRI-011381 hydrochloride has important application value in the study of tissue repair and fibrotic diseases[3].
In vitro, SRI-011381 hydrochloride (10μM) treatment of mouse lung fibroblasts for 48h promoted cell proliferation and increased the expression of intracellular TGF-β1, neutrophil alkaline phosphatase 3 (NALP3), collagen-1, and α-smooth muscle actin (α-SMA) proteins[4].
In vivo, SRI-011381 hydrochloride (30mg/kg) was intraperitoneally injected into rats with heart failure (HF) model, which reversed the protective effect of SMOC2 knockdown (sh-SMOC2) against HF, aggravated cardiac injury and fibrosis, and reversed the regulation of p-Smad3, p62, LC3-II/I, and Beclin-1 by sh-SMOC2[5]. SRI-011381 hydrochloride (30mg/kg) was intraperitoneally injected into YAPGFAP-CKO mice with experimental autoimmune encephalomyelitis (EAE), which inhibited inflammatory infiltration, alleviated neuronal loss, and partially rescued the optic nerve and retinal defects of mice[6].
References:
[1] Wang J, Yang L, Mei J, et al. Knockdown of notch suppresses epithelial-mesenchymal transition and induces angiogenesis in oral submucous fibrosis by regulating TGF-β1[J]. Biochemical Genetics, 2024, 62(2): 1055-1069.
[2] Moustakas A, Pardali K, Gaal A, et al. Mechanisms of TGF-β signaling in regulation of cell growth and differentiation[J]. Immunology letters, 2002, 82(1-2): 85-91.
[3] Yao C, Zhou X, Weng W, et al. Aligned nanofiber nerve conduits inhibit alpha smooth muscle actin expression and collagen proliferation by suppressing TGF-β1/SMAD signaling in traumatic neuromas[J]. Experimental and Therapeutic Medicine, 2021, 22(6): 1414.
[4] Han J, Jia Y, Wang S, et al. The improvement effect of sodium ferulate on the formation of pulmonary fibrosis in silicosis mice through the neutrophil alkaline phosphatase 3 (NALP3)/transforming growth factor-β1 (TGF-β1)/α-smooth muscle actin (α-SMA) pathway[J]. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2021, 27: e927978-1.
[5] Ren Y, Wu Y, He W, et al. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy[J]. Open Medicine, 2023, 18(1): 20230752.
[6] Wu Q, Miao X, Zhang J, et al. Astrocytic YAP protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model through TGF-β signaling[J]. Theranostics, 2021, 11(17): 8480.
SRI-011381 hydrochloride是一种具口服活性的转化生长因子β（TGF-β）信号通路的激活剂，具有神经保护作用[1]。TGF-β是一种多效的细胞因子，可调节细胞生长和分化、凋亡、细胞运动、细胞外基质的产生、血管生成和细胞免疫反应[2]。SRI-011381 hydrochloride在组织修复、纤维化疾病研究中具有重要应用价值[3]。
在体外，SRI-011381 hydrochloride（10μM）处理小鼠肺成纤维细胞48h，促进了细胞增殖，增加了细胞内TGF-β1、中性粒细胞碱性磷酸酶3（NALP3）、胶原蛋白-1和α-平滑肌肌动蛋白（α-SMA）蛋白的表达[4]。
在体内，SRI-011381 hydrochloride（30mg/kg）通过腹腔注射治疗心力衰竭（HF）模型大鼠，逆转了SMOC2敲低（sh-SMOC2）对HF的保护作用，加重了心脏损伤和纤维化，逆转了sh-SMOC2对p-Smad3、p62、LC3-II/I和Beclin-1的调控[5]。SRI-011381 hydrochloride（30mg/kg）通过腹腔注射治疗患有实验性自身免疫性脑脊髓炎（EAE）的YAPGFAP-CKO小鼠，抑制了炎症浸润，减轻了神经元丢失，部分挽救了小鼠的视神经和视网膜缺陷[6]。