Gore-Hyer Elizabeth, Shegogue Daniel, Markiewicz Malgorzata, Lo Shianlen, Hazen-Martin Debra, Greene Eddie L, Grotendorst Gary, Trojanowska Maria
Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston 29425, USA.
Am J Physiol Renal Physiol. 2002 Oct;283(4):F707-16. doi: 10.1152/ajprenal.00007.2002.
Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-beta and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-beta and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, alpha(2)(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-beta and CTGF in HMCs. However, only TGF-beta stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-beta and CTGF, although TGF-beta was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.
转化生长因子-β（TGF-β）和结缔组织生长因子（CTGF）在各种形式的组织纤维化中均有广泛表达，包括肾脏纤维化疾病。为了阐明这些生长因子在肾纤维化过程中负责病理性细胞外基质（ECM）沉积的细胞中的共同作用和不同作用，研究了TGF-β和CTGF对原代人系膜细胞（HMCs）和人近端肾小管上皮细胞（HTECs）中ECM表达的影响。在HMCs中，TGF-β和CTGF均以相似的效力显著诱导胶原蛋白表达。此外，TGF-β和CTGF在HMCs中同样诱导α2（I）-胶原蛋白启动子活性和mRNA水平。然而，只有TGF-β刺激HTECs中的胶原蛋白合成。肌腱蛋白-C（TN-C）在HTECs中的表达受到TGF-β和CTGF的上调，尽管TGF-β是更强效的诱导剂。因此，这两种生长因子对HMCs中ECM产生具有相似的促纤维化作用，而在HTECs中发挥不同作用。CTGF诱导TN-C（上皮-间质转分化（EMT）的标志物），而在HTECs中未显著诱导胶原蛋白合成，这可能表明CTGF在EMT中发挥更主要的作用，而非在肾纤维化期间诱导HTECs过度沉积胶原蛋白。
