SCGB1A1

Fig1. The production of T-helper cell type 2 cytokines such as IL-4 and IL-13 or infection with rhinovirus suppresses expression of FOXA2 in club cells. (Rachel Warren, 2019)

What is SCGB1A1 protein?

SCGB1A1 (secretoglobin family 1A member 1) gene is a protein coding gene which situated on the long arm of chromosome 11 at locus 11q12. SCGB1A1, also known as uteroglobin, is a secreted, small molecular weight protein that is a member of the secretoglobin superfamily. This protein was originally found in the uterine secretions of mice, hence the name uteroglobinin, but it was later found to be expressed in a variety of tissues and cell types. SCGB1A1 has anti-inflammatory and immunomodulatory effects and is able to reduce the inflammatory response by inhibiting the activity of inflammatory cells. The SCGB1A1 protein is consisted of 91 amino acids and its molecular mass is approximately 10.0 kDa.

What is the function of SCGB1A1 protein?

SCGB1A1 is mainly expressed in human epithelial cells of respiratory tract, urogenital tract and gastrointestinal tract, and has a variety of biological functions. It has anti-inflammatory and immunomodulatory effects, which can inhibit the release of inflammatory cytokines and reduce the inflammatory response. SCGB1A1 also has antimicrobial activity, which can inhibit and kill bacteria and participate in the body's natural immune response. In addition, SCGB1A1 also plays a role in tumor monitoring, and changes in its expression levels are associated with certain types of cancer, so it may serve as a biomarker for cancer.

SCGB1A1 Related Signaling Pathway

SCGB1A1 plays an important role in the immune and inflammatory response of the lung and can influence the development and function of Alveolar Macrophages (AMs). Studies have shown that SCGB1A1 regulates biological pathways associated with antigen presentation, antiviral immunity, and inflammation. In the absence of the SCGB1A1 gene, these pathways are significantly down-regulated, leading to early activation of inflammatory pathways, and the SCGB1A1 protein is able to reduce the response of alveolar macrophages to microbial stimulation and reduce the release of cytokines and chemokines. Such as IL-1β, IL-6, IL-8, MIP-1α, TNF-α, and MCP-1. In addition, SCGB1A1 is also involved in the regulation of Notch signaling pathway, which plays a role in the transdifferentiation of club cells and BASCs (bronchoalveolar stem cells) into AT2 cells. Activation or inhibition of Notch signaling pathway has opposite regulatory effects on the differentiation of these two types of cells.

SCGB1A1 Related Diseases

Abnormal SCGB1A1 protein is associated with chronic obstructive pulmonary disease (COPD), and its expression is reduced in COPD patients. In addition, SCGB1A1 is associated with diseases such as Silicosis and Bronchiolitis Obliterans. In patients with asthma, FOXA2 expression downstream of SCGB1A1 is reduced, suggesting that it may play a role in the pathogenesis of asthma. The SCGB1A1 protein may also be implicated in atopic diseases, such as allergic rhinitis and eczema, which involve the IL21R gene, which is associated with the innate immune system and TGF-Beta signaling pathway. In addition, SCGB1A1 protein plays a role in the inflammatory and immune response of Alveolar Macrophages (AMs), affecting the defense against respiratory infections, and its deficiency may lead to early activation of inflammatory pathways and increased cytokine release.

Bioapplications of SCGB1A1

Because SCGB1A1 has significant anti-inflammatory effects, it may be developed as a drug to treat various inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. The expression level of SCGB1A1 varies in some diseases, so it may serve as a biomarker to diagnose these diseases and aid in early detection and disease surveillance.

Case Study 1: Ruixi Zhou, 2019

Sepsis has a high in clinic neonatal mortality. Moreover, a considerable number of children's brains remain affected even after the treatment of sepsis and it often leaves sequelae. Therefore, early intervention for sepsis is of considerable significance. Recent studies have shown that Club cell protein (CC16) is closely related to the p38 mitogen-activated protein kinase (MAPK) signaling pathway, which can regulate inflammation, oxidative stress, apoptosis, and autophagy during sepsis. Thus, the researchers analyzed the neuroprotective effect of recombinant CC16 (rCC16) in a neonatal sepsis rat model. For the first time, they found that the p38MAPK signaling pathway was activated in neonatal brain tissue of rats with sepsis, and the CC16 levels decreased significantly. Secondly, after the rCC16 interference, the occurrence of inflammation, oxidative stress and apoptosis were subsequently reversed, and autophagy was further stimulated. Finally, through further intervention using the p38MAPK signaling pathway inhibitor, SB203580, or its agonist, anisomycin, they confirmed that rCC16 reduced rat mortality and improve general conditions. Simultaneously, it had also neuroprotective effect. Its mechanism could be related to oxidative stress, inflammation, and apoptosis reduced and autophagy activated by rCC16 inhibiting the p38MAPK signaling pathway.

Fig1. Vital signs at 12 h after operation for each group.

Fig2. Effect of rCC16 treatment on the pathological changes in CLP rats at 12 h.

Case Study 2: Min Pang, 2015

Clara cell protein (CC16) is a well-known anti-inflammatory protein secreted by the epithelial Clara cells of the airways. Previous studies suggest that CC16 gene transfer suppresses expression of interleukin (IL)-8 in bronchial epithelial cells. However, its role in the function of these cells during inflammation is not well understood. This study evaluated the effect of CC16 on the expression of matrix metalloproteinase (MMP)-9 in lipopolysaccharide (LPS)-stimulated rat tracheal epithelial cells and its underlying molecular mechanisms. The researchers generated recombinant rat CC16 protein (rCC16) which was bioactive in inhibiting the activity of phospholipase A2. rCC16 inhibited LPS-induced MMP-9 expression at both mRNA and protein levels in a concentration-dependent (0-2 μg/mL) manner, as demonstrated by real time RT-PCR, ELISA, and zymography assays. Gene transcription and DNA binding studies demonstrated that rCC16 suppressed LPS-induced NF-κB activation and its binding of gene promoters as identified by luciferase reporter and gel mobility shift assays, respectively. Western blotting and immunofluorescence staining analyses further revealed that rCC16 concentration dependently inhibited the effects of LPS on nuclear increase and cytosol reduction of NF-κB, on the phosphorylation and reduction of NF-κB inhibitory IκBα, and on p38 MAPK-dependent NF-κB activation by phosphorylation at Ser276 of its p65 subunit.

Fig3. Acid–base titration analysis shows concentration-dependent inhibition of PLA2 activity by rCC16.

Fig4. rCC16 inhibits LPS-induced phosphorylation of IκBα in RTE cells.

SCGB1A1 has several biochemical functions, for example, . Some of the functions are cooperated with other proteins, some of the functions could acted by SCGB1A1 itself. We selected most functions SCGB1A1 had, and list some proteins which have the same functions with SCGB1A1. You can find most of the proteins on our site.

SCGB1A1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SCGB1A1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SCGB1A1.