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1.
结缔组织生长因子(CTGF/CCN2)属于即刻早期基因编码的CCN家族中的一员,参与正常细胞增殖、黏附、迁移、凋亡及新生血管形成,在创伤修复、纤维化疾病和肿瘤形成中也具有重要的作用。新近研究发现,CTGF在肺癌组织中表达较正常肺组织降低,与肺癌的发生、发展密切相关,被视为肺癌转移和预后的评价指标。本文简要介绍了CTGF的结构、功能及在其肺癌中的研究进展,以期为肺癌的临床治疗提供新的思路。 相似文献
2.
Lau LF 《Cellular and molecular life sciences : CMLS》2011,68(19):3149-3163
CCN1 (CYR61) is a dynamically expressed, multifunctional matricellular protein that plays essential roles in cardiovascular
development during embryogenesis, and regulates inflammation, wound healing and fibrogenesis in the adult. Aberrant CCN1 expression
is associated with myriad pathologies, including various cancers and diseases associated with chronic inflammation. CCN1 promotes
diverse and sometimes opposing cellular responses, which can be ascribed, as least in part, to disparate activities mediated
through its direct binding to distinct integrins in different cell types and contexts. Accordingly, CCN1 promotes cell proliferation,
survival and angiogenesis by binding to integrin αvβ3, and induces apoptosis and senescence through integrin α6β1 and heparan sulfate proteoglycans. The ability of CCN1 to trigger the accumulation of a robust and sustained level of reactive
oxygen species underlies some of its unique activities as a matrix cell-adhesion molecule. Emerging studies suggest that CCN1
might be useful as a biomarker or therapeutic target in certain diseases. 相似文献
3.
Dafne Gays Massimo Mattia Santoro 《Cellular and molecular life sciences : CMLS》2013,70(14):2489-2503
MicroRNAs are small non-coding RNAs endogenously expressed by all tissues during development and adulthood. They regulate gene expression by controlling the stability of targeted messenger RNA. In cardiovascular tissues microRNAs play a role by modulating essential genes involved in heart and blood vessel development and homeostasis. The zebrafish (Danio rerio) system is a recognized vertebrate model system useful to study cardiovascular biology; recently, it has been used to investigate microRNA functions during natural and pathological states. In this review, we will illustrate the advantages of the zebrafish model in the study of microRNAs in heart and vascular cells, providing an update on recent discoveries using the zebrafish to identify new microRNAs and their targeted genes in cardiovascular tissues. Lastly, we will provide evidence that the zebrafish is an optimal model system to undercover new microRNA functions in vertebrates and to improve microRNA-based therapeutic approaches. 相似文献
4.
Elke Winterhager Alexandra Gellhaus 《Cellular and molecular life sciences : CMLS》2014,71(12):2299-2311
The CCN family of proteins consists of six high homologous matricellular proteins which act predominantly by binding to heparin sulphate proteoglycan and a variety of integrins. Interestingly, CCN proteins are regulated by ovarian steroid hormones and are able to adapt to changes in oxygen concentration, which is a necessary condition for successful implantation. CCN1 is involved in processes of angiogenesis within reproductive systems, thereby potentially contributing to diseases such as endometriosis and disturbed angiogenesis in the placenta and fetus. In the ovary, CCN2 is the key factor for follicular development, ovulation and corpora luteal luteolysis, and its deletion leads to fertility defects. CCN1, CCN2 and CCN3 seem to be regulators for human trophoblast proliferation and migration, but with CCN2 acting as a counterweight. Alterations in the expression of these three proteins could contribute to the shallow invasion properties observed in preeclampsia. Little is known about the role of CCN4–6 in the reproductive organs. The ability of CCN1, CCN2 and CCN3 to interact with numerous receptors enables them to adapt their biological function rapidly to the continuous remodelling of the reproductive organs and in the development of the placenta. The CCN proteins mediate their specific cell physiological function through the receptor type of their binding partner followed by a defined signalling cascade. Because of their partly overlapping expression patterns, they could act in a concert synergistically or in an opposite way within the reproductive organs. Imbalances in their expression levels are correlated to different human reproductive diseases, such as endometriosis and preeclampsia. 相似文献
5.
6.
The neurotrophic factors in non-neuronal tissues 总被引:17,自引:0,他引:17
Sariola H 《Cellular and molecular life sciences : CMLS》2001,58(8):1061-1066
Although neurotrophic factors are defined as molecules that maintain neuronal cells, they possess a range of functions outside
the nervous system. For example, glial cell line-derived neurotrophic factor is essential for ureteric branching in kidney
morphogenesis and for regulating the fate of stem cells during spermatogenesis. Leukemia inhibitory factor, a member of the
interleukin-6 (IL-6) ciliary neurotrophic factor family, inhibits differentiation of embryonic stem cells, induces tubulogenesis
in the embryonic kidney, and regulates sperm differentiation. Other IL-6 family members are important in cardiac differentiation
and they have pleiotropic functions in the hematopoietic and immune systems. Although neurotrophin receptors have been found
on a number of non-neuronal tissues, they represent mostly truncated receptor isoforms that are incapable of signal transduction
and may have scavenger or dominant negative functions. However, several examples can be presented of essential non-neuronal
functions played by neurotrophins in e.g., cardiac, hair follicle, and vascular differentiation, and the maintenance of immune
cells. 相似文献
7.
Pierfrancesco Pagella Lucia Jiménez-Rojo Thimios A. Mitsiadis 《Cellular and molecular life sciences : CMLS》2014,71(12):2241-2251
The head is innervated by 12 cranial nerves (I–XII) that regulate its sensory and motor functions. Cranial nerves are composed of sensory, motor, or mixed neuronal populations. Sensory neurons perceive generally somatic sensations such as pressure, pain, and temperature. These neurons are also involved in smell, vision, taste, and hearing. Motor neurons ensure the motility of all muscles and glands. Innervation plays an essential role in the development of the various orofacial structures during embryogenesis. Hypoplastic cranial nerves often lead to abnormal development of their target organs and tissues. For example, Möbius syndrome is a congenital disease characterized by defective innervation (i.e., abducens (VI) and facial (VII) nerves), deafness, tooth anomalies, and cleft palate. Hence, it is obvious that the peripheral nervous system is needed for both development and function of orofacial structures. Nerves have a limited capacity to regenerate. However, neural stem cells, which could be used as sources for neural tissue maintenance and repair, have been found in adult neuronal tissues. Similarly, various adult stem cell populations have been isolated from almost all organs of the human body. Stem cells are tightly regulated by their microenvironment, the stem cell niche. Deregulation of adult stem cell behavior results in the development of pathologies such as tumor formation or early tissue senescence. It is thus essential to understand the factors that regulate the functions and maintenance of stem cells. Yet, the potential importance of innervation in the regulation of stem cells and/or their niches in most organs and tissues is largely unexplored. This review focuses on the potential role of innervation in the development and homeostasis of orofacial structures and discusses its possible association with stem cell populations during tissue repair. 相似文献
8.
More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell
from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular
matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration,
and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized,
opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles
in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during
development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components
with a special emphasis on embryonic and adult stem cells and their niches. 相似文献
9.
Jedrzejas MJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2799-2822
Bacteria present a variety of molecules either on their surface or in a cell-free form. These molecules take part in numerous
processes in the interactions with their host, with its tissues and other molecules. These molecules are essential to bacterial
pathogenesis either during colonization or the spread/invasion stages, and most are virulence factors. This review is focused
on such molecules using Streptococcus pneumoniae, a Gram-positive bacterium, as an example. Selected surface proteins are introduced, their structure described, and, whenever
available, their mechanisms of function on an atomic level are explained. Such mechanisms for hyaluronate lyase, pneumococcal
surface protein A, pneumolysin, histidine-triad and fibronectin-binding proteins are discussed. Elucidation of molecular mechanisms
of virulence factors is essential for the understanding of bacteria and their functional properties. Structural biology appears
pivotal for these studies, as structural and mechanistic insights facilitate rational approach to the development of new treatments.
Received 12 March 2007; received after revision 28 June 2007; accepted 18 July 2007 相似文献
10.
Catherine Kirn-Safran Mary C. Farach-Carson Daniel D. Carson 《Cellular and molecular life sciences : CMLS》2009,66(21):3421-3434
Heparan sulfate proteoglycans are a remarkably diverse family of glycosaminoglycan-bearing protein cores that include the
syndecans, the glypicans, perlecan, agrin, and collagen XVIII. Members of this protein class play key roles during normal
processes that occur during development, tissue morphogenesis, and wound healing. As key components of basement membranes
in organs and tissues, they also participate in selective filtration of biological fluids, in establishing cellular barriers,
and in modulation of angiogenesis. The ability to perform these functions is provided both by the features of the protein
cores as well as by the unique properties of heparan sulfate, which is assembled as a polymer of N-acetylglucosamine and glucuronic acid and modified by specific enzymes to generate specialized biologically active structures.
This article discusses the structures and functions of this amazing family of proteoglycans and provides a platform for further
study of the individual members. 相似文献
11.
Melanocortin receptors: their functions and regulation by physiological agonists and antagonists 总被引:14,自引:0,他引:14
Abdel-Malek ZA 《Cellular and molecular life sciences : CMLS》2001,58(3):434-441
The melanocortins are a family of bioactive peptides derived from proopiomelanocortin, and share significant structural similarity.
Those peptides are best known for their stimulatory effects on pigmentation and steroidogenesis. Melanocortins are synthesized
in various sites in the central nervous system and in peripheral tissues, and participate in regulating multiple physiological
functions. Research during the past decade has provided evidence that melanocortins elicit their diverse biological effects
by binding to a distinct family of G protein-coupled receptors with seven transmembrane domains. To date, five melanocortin
receptor genes have been cloned and characterized. Those receptors differ in their tissue distribution and in their ability
to recognize the various melanocortins and the physiological antagonists, agouti signaling protein and agouti-related protein.
These advances have opened new horizons for exploring the significance of melanocortins, their antagonists, and their receptors
in a variety of important physiological functions.
Received 5 October 2000; accepted 10 November 2000 相似文献
12.
Carboxypeptidases from A to Z: implications in embryonic development and Wnt binding 总被引:4,自引:0,他引:4
Carboxypeptidases perform many diverse functions in the body. The well-studied pancreatic enzymes (carboxypeptidases A1, A2 and B) are involved in the digestion of food, whereas a related enzyme (mast-cell carboxypeptidase A) functions in the degradation of other proteins. Several members of the metallocarboxypeptidase gene family (carboxypeptidases D, E, M and N) are more selective enzymes and are thought to play a role in the processing of intercellular peptide messengers. Three other members of the metallocarboxypeptidase gene family do not appear to encode active enzymes; these members have been designated CPX-1, CPX-2 and AEBP1/ACLP. In this review, we focus on the recently discovered carboxypeptidase Z (CPZ). This enzyme removes C-terminal Arg residues from synthetic substrates, as do many of the other members of the gene family. However, CPZ differs from the other enzymes in that CPZ is enriched in the extracellular matrix and is broadly distributed during early embryogenesis. In addition to containing a metallocarboxypeptidase domain, CPZ also contains a Cys-rich domain that has homology to Wnt-binding proteins; Wnts are important signaling molecules during development. Although the exact function of CPZ is not yet known, it is likely that this protein plays a role in development by one of several possible mechanisms. 相似文献
13.
The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy. 相似文献
14.
Kristin T. Jacobsen Kerstin Iverfeldt 《Cellular and molecular life sciences : CMLS》2009,66(14):2299-2318
The Alzheimer’s amyloid precursor protein (APP) belongs to a conserved gene family that also includes the mammalian APLP1
and APLP2, the Drosophila APPL, and the C. elegans APL-1. The biological function of APP is still not fully clear. However, it is known that the APP family proteins have redundant
and partly overlapping functions, which demonstrates the importance of studying all APP family members to gain a more complete
picture. When APP was first cloned, it was speculated that it could function as a receptor. This theory has been further substantiated
by studies showing that APP and its homologues bind both extracellular ligands and intracellular adaptor proteins. The APP
family proteins undergo regulated intramembrane proteolysis (RIP), generating secreted and cytoplasmic fragments that have
been ascribed different functions. In this review, we will discuss the APP family with focus on biological functions, binding
partners, and regulated processing. 相似文献
15.
Jessica L. Bell Kristin Wächter Britta Mühleck Nikolaos Pazaitis Marcel Köhn Marcell Lederer Stefan Hüttelmaier 《Cellular and molecular life sciences : CMLS》2013,70(15):2657-2675
The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, IGF2BP3) belong to a conserved family of RNA-binding, oncofetal proteins. Several studies have shown that these proteins act in various important aspects of cell function, such as cell polarization, migration, morphology, metabolism, proliferation and differentiation. In this review, we discuss the IGF2BP family’s role in cancer biology and how this correlates with their proposed functions during embryogenesis. IGF2BPs are mainly expressed in the embryo, in contrast with comparatively lower or negotiable levels in adult tissues. IGF2BP1 and IGF2BP3 have been found to be re-expressed in several aggressive cancer types. Control of IGF2BPs’ expression is not well understood; however, let-7 microRNAs, β-catenin (CTNNB1) and MYC have been proposed to be involved in their regulation. In contrast to many other RNA-binding proteins, IGF2BPs are almost exclusively observed in the cytoplasm where they associate with target mRNAs in cytoplasmic ribonucleoprotein complexes (mRNPs). During development, IGF2BPs are required for proper nerve cell migration and morphological development, presumably involving the control of cytoskeletal remodeling and dynamics, respectively. Likewise, IGF2BPs modulate cell polarization, adhesion and migration in tumor-derived cells. Moreover, they are highly associated with cancer metastasis and the expression of oncogenic factors (KRAS, MYC and MDR1). However, a pro-metastatic role of IGF2BPs remains controversial due to the lack of ‘classical’ in vivo studies. Nonetheless, IGF2BPs could provide valuable targets in cancer treatment with many of their in vivo roles to be fully elucidated. 相似文献
16.
Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less ‘traditional’ functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2–4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4–7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these ‘non-traditional’, often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular VEGF function will be described. This review is only concerned with homeostatic functions of VEGF in the normal, non-injured brain. The reader is referred elsewhere in this series for a review on VEGF actions in response to various forms of brain injury and/or brain pathology. 相似文献
17.
Insect chitinase and chitinase-like proteins 总被引:6,自引:0,他引:6
Yasuyuki Arakane Subbaratnam Muthukrishnan 《Cellular and molecular life sciences : CMLS》2010,67(2):201-216
Insect chitinases belong to family 18 glycosylhydrolases that hydrolyze chitin by an endo-type of cleavage while retaining
the anomeric β-(1→4) configuration of products. There are multiple genes encoding chitinases and chitinase-like proteins in
all insect species studied using bioinformatics searches. These chitinases differ in size, domain organization, physical,
chemical and enzymatic properties, and in patterns of their expression during development. There are also differences in tissue
specificity of expression. Based on a phylogenetic analysis, insect chitinases and chitinase-like proteins have been classified
into several different groups. Results of RNA interference experiments demonstrate that at least some of these chitinases
belonging to different groups serve non-redundant functions and are essential for insect survival, molting or development.
Chitinases have been utilized for biological control of insect pests on transgenic plants either alone or in combination with
other insecticidal proteins. Specific chitinases may prove to be useful as biocontrol agents and/or as vaccines. 相似文献
18.
19.
G. E. Callander R. A. D. Bathgate 《Cellular and molecular life sciences : CMLS》2010,67(14):2327-2341
Since its discovery in the 1920s, relaxin has enjoyed a reputation as a peptide hormone of pregnancy. However, relaxin and
other relaxin family peptides are now associated with numerous non-reproductive physiologies and disease states. The new millennium
bought with it the sequence of the human genome and subsequently new directions for relaxin research. In 2002, the ancestral
relaxin gene RLN3 was identified from genome databases. The relaxin-3 peptide is highly expressed in a small region of the brain and in species
from teleost to primates and has both conserved sequence and sites of expression. Combined with the discovery of the relaxin
family peptide receptors, interest in the role of the relaxin family peptides in the central nervous system has been reignited.
This review explores the relaxin family peptides that are expressed in or act upon the brain, the receptors that mediate their
actions, and what is currently known of their functions. 相似文献
20.
I. Dutriez N. Salès M. -C. Fournié-Zaluski B. P. Roques 《Cellular and molecular life sciences : CMLS》1992,48(3):290-300
Neutral endopeptidase (NEP, enkephalinase, CALLA) which is present in various neural and non-neural tissues, is able to cleave a variety of regulatory peptides. The distribution of NEP has been studied during rat pre-and post-natal development by autoradiography after in vitro binding of the tritiated inhibitor [3H]HACBO-Gly to whole-body and organ sections. In the central nervous system (CNS), where the presence of NEP has been related to the termination of the action of enkephalins, the external layer of the olfactory bulbs is the only structure prominently labeled before birth. Other CNS structures rich in NEP in the adult, such as the nigrostriatal tract, are progressively labeled after birth. Outside the CNS, the progressive appearance of NEP in the kidney, the lungs and the salivary glands suggests its concomitant involvement in adult physiological functions, including fluid balance control, possibly by cleaving the atrial natriuretic peptide (ANP) and other peptides. On the other hand, transient or enhanced expression of NEP is observed during the development of several organs such as the sensory organs, the heart and the major blood vessels, the intestine, the bones and the genital tubercle. In addition to the still incompletely known physiological functions of the enzyme, the developmental pattern of its expression in several tissues strongly suggests a modulatory role for NEP in the ontogeny of a large number of organs. 相似文献